Clinical efficacy of bronchodilators in equine asthma: Looking for minimal important difference.

BACKGROUND: Airway obstruction is the main trait of severe equine asthma that affects respiratory function and elicits detrimental effects on clinical presentation. Only few and underpowered clinical studies have investigated the impact of improvement in lung function induced by bronchodilators on the clinical signs of asthma-affected horses. OBJECTIVES: To identify the minimal important difference (MID) in lung function elicited by bronchodilator leading to a meaningful improvement in clinical signs. STUDY DESIGN: Pairwise meta-analysis and meta-regression analysis. METHODS: Literature searches were performed for studies that investigated the effect of bronchodilator therapy on lung function and clinical condition of asthmatic horses. The relationship between the change in lung function variables and clinical score was analysed via random-effect meta-regression. One-point change of the Improved clinically Detectable Equine Asthma Scoring System (IDEASS) score was used to identify the MID. RESULTS: A significant (P<0.05) relationship was found between the changes in IDEASS score and maximum change in transpulmonary pressure (ΔPplmax ) or pulmonary resistance (RL ). Since only the model resulting for RL passed through the origin (Y-intercept when X = 0: -0.31, 95% CI -0.75 to 0.14), this variable was used to identify the MID correlated with a meaningful improvement in clinical signs. The resulting MID value was a change in RL of 0.63 cm H2 O/L/s (95% CI 0.33-0.94), representing the slope of meta-regression model (high quality of evidence). MAIN LIMITATIONS: No long-term studies investigated the effect of bronchodilator agents on both lung function and clinical signs in asthmatic horses. CONCLUSIONS: In conclusion, bronchodilator pharmacotherapy in equine asthma elicits clinically meaningful effect when RL increases ≥1 cm H2 O/L/s, a value indicating the MID. Assessing the MID based on change in RL may improve the quality of evidence and the scientific impact of future clinical trials as it extends beyond the simple, and limiting, evaluation of statistical significance.

The caloric irrigation test.

The test of caloric thermal irrigations is one of the first tests for sensitivity of the peripheral vestibular systems dating to the late 1800s. This chapter reviews the various protocols that have been developed over the years using thermal irrigations to the external auditory canals. The discussion covers the interpretations of the protocols and makes recommendations for those protocols that have the best performance and at the same time are practical to perform. The primary utility of the caloric test has remained the same since its origination - the comparison of the relative sensitivity of the right versus left peripheral vestibular function. This is now known to be applicable to the horizontal canals without any significant influence of the vertical canals. The hypothesized physiology behind the thermal caloric proposed in the early 1900s has now, with the help of experiments in microgravity, been partially verified. Until recently this was the only test that could investigate one peripheral end organ at a time. It is still the one test that emphasizes the low-frequency function of the horizontal canals individually.

Safety and efficacy of kunzea oil-containing formulations for the management of psoriasis: a randomized, controlled trial.

WHAT IS KNOWN AND OBJECTIVE: Anecdotally, topical kunzea oil has been used to treat various skin conditions, including psoriasis and eczema, with good results. This study compared the clinical efficacy of kunzea oil (20%)-containing formulations in mild to moderate psoriasis. METHODS: A randomized, comparative, double-blind, 8-week study was undertaken. Thirty patients (age range: 25-74 years and mean ± SD: 52·8 ± 13·6 years) with mild to moderate psoriasis (affecting at least 10% of one or more body regions: arms, head, legs and trunk) randomly received ointment and/or scalp lotion containing 20% kunzea oil (test group) or control medications not containing kunzea oil (control group). Formulations in both treatment arms also contained 5% liquor carbonis detergens (LCD) and 3% salicylic acid. The clinical responses to the test and control formulations were evaluated using the Psoriasis Area and Severity Index (PASI). RESULTS AND DISCUSSION: After 8 weeks of treatment, both test and control groups demonstrated a significant (P < 0·05) improvement in PASI scores. Subjects in the test group had a decrease in mean±SD PASI score from 12·7 ± 7·9 to 6·7 ± 7·2, whereas the control group showed a decrease in PASI score from 8·1 ± 4·6 to 3·5 ± 4·7. Comparative efficacy analysis between the test and control groups did not reveal any significant difference (P > 0·05). WHAT IS NEW AND CONCLUSIONS: The inclusion of kunzea oil made no difference to the efficacy of topical formulations containing LCD and salicylic acid for the treatment of psoriasis.

Zebrafish--on the move towards ophthalmological research.

Millions of people are affected by visual impairment and blindness globally, and the prevalence of vision loss is likely to increase as we are living longer. However, many ocular diseases remain poorly controlled due to lack of proper understanding of the pathogenesis and the corresponding lack of effective therapies. Consequently, there is a major need for animal models that closely mirror the human eye pathology and at the same time allow higher-throughput drug screening approaches. In this context, zebrafish as an animal model organism not only address these needs but can in many respects reflect the human situation better than the current rodent models. Over the past decade, zebrafish have become an established model to study a variety of human diseases and are more recently becoming a valuable tool for the study of human ophthalmological disorders. Many human ocular diseases such as cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration have already been modelled in zebrafish. In addition, zebrafish have become an attractive model for pre-clinical drug toxicity testing and are now increasingly used by scientists worldwide for the discovery of novel treatment approaches. This review presents the advantages and uses of zebrafish for ophthalmological research.

Randomized controlled trial of the effect of depth of anaesthesia on postoperative pain.

BACKGROUND: Our hypothesis was that deep anaesthesia, as estimated by a low target bispectral index (BIS) of 30-40, would result in less postoperative pain than that achieved at a conventional depth of anaesthesia. METHODS: We undertook a randomized double-blind controlled study at two tertiary teaching hospitals in New Zealand (2010-1) recruiting 135 adult patients ASA I-II presenting for non-emergent surgery under general anaesthesia requiring tracheal intubation. Anaesthesia was maintained with desflurane and a multimodal analgesia regimen comprising fentanyl infusion, i.v. paracetamol, and parecoxib. Patients were randomly assigned to either a low BIS (30-40) group or a high BIS (45-60) group. Desflurane concentrations were titrated to achieve these targets. Postoperative pain was assessed by: the pain on awakening (0-10, verbal rating scale, VRS(awake)) in the post-anaesthetic care unit; pain on activity at 20-24 h after operation (VRS(d1A)); and the rate of morphine patient-controlled analgesia (PCA) usage over the first 24 h. RESULTS: There was no statistically significant difference between the two groups for any of the pain scores. The median [inter-quartile range (IQR)] VRS(awake) was 4.0 (0-8) for the low and 4.0 (0-8) for the high BIS groups (P=0.56). The median (IQR) VRS(d1A) was 3.0 (1-5) for the low and 3.0 (1.5-4.5) for the high BIS groups (P=0.83). The median PCA morphine consumption in the low BIS group was 0.61 mg h(-1) (0.04-1.5) vs 0.43 mg h(-1) (0-1.59) in the high BIS group (P=0.98). CONCLUSIONS: We conclude that there is no clinically useful analgesic effect of a deep anaesthesia regimen.

Changing climate and sea level alter Hg mobility at Lake Tulane, Florida, U.S.

Between 45,000 cal years BP and the beginning of the Holocene, the accumulation rate for Hg in sediments of Lake Tulane, Florida ranged from ≈2 to 10 µg m(-2) yr(-1), compared with 53 µg Hg m(-2) yr(-1) in the 1985-1990 period of anthropogenic input. The locality experienced regional draw-down of the water table during the Wisconsinan glaciation, which lowered global sea level by nearly 130 m. Natural atmospheric deposition of Hg to the surrounding area resulted in long-term (ca. 100,000 years) sequestration of this atmospheric flux of Hg, primarily by adsorption in the oxic Al- and Fe-hydroxide-rich sandy subsoil. Global sea level rise during deglaciation led to a rising regional water table, flooding the oxidized soils surrounding Tulane. Iron and adsorbed Hg were mobilized by reductive dissolution and transported by groundwater flow to Lake Tulane and ultimately to the accumulating sediment. The accumulation rate of Hg (and Fe) increased rapidly about 16,000 cal years BP, peaked at nearly 60 µg Hg m(-2) yr(-1) ca. 13,000-14,000 cal years BP, declined sharply during the Younger Dryas, and then increased sharply to a second 60 µg Hg m(-2) yr(-1) peak about 5000 cal years BP. Thereafter, it declined nearly to background by 900 cal years BP. In similar geologic situations, rapid modern sea level rise will initiate this process globally, and may mobilize large accumulations of Hg and lesser amounts of As, and other redox sensitive metals to groundwater and surface water.

Structural characteristics of adenohypophysis in hypertensive ISIAH rats in early ontogeny.

Comparative morphological study of the adenohypophysis was conducted in 3-week-old normotensive WAG and hypertensive ISIAH rats (prehypertension period) to elucidate the role of the adenohypophysis in the development of essential hypertension. Morphometric analysis revealed ultrastructural signs of functional activation of somatotrophs, gonadotrophs, and corticotrophs in ISIAH rats. These peculiarities of structural organization of adenohypophysis in hypertensive rats can attest to enhanced response of the hypothalamic-pituitary-adrenal axis in these animals to natural stress associated with their transition to independent feeding. Increased stress sensitivity during the prehypertensive period of postnatal ontogeny contributes to the development of arterial hypertension.

Single-mode fiber, velocity interferometry.

In this paper, we describe a velocity interferometer system based entirely on single-mode fiber optics. This paper includes a description of principles used in developing the single-mode velocity interferometry system (SMV). The SMV design is based on polarization-insensitive components. Polarization adjusters are included to eliminate the effects of residual birefringence and polarization dependent losses in the interferometers. Characterization measurements and calibration methods needed for data analysis and a method of data analysis are described. Calibration is performed directly using tunable lasers. During development, we demonstrated its operation using exploding-foil bridge-wire fliers up to 200 m/s. In a final test, we demonstrated the SMV in a gas gun experiment up to 1.2 km/sec. As a basis for comparison in the gas gun experiment, we used another velocimetry technique that is also based on single-mode fiber optics: photonic Doppler velocimetry (PDV). For the gas gun experiment, we split the light returned from a single target spot and performed a direct comparison of the homodyne (SMV) and heterodyne (PDV) techniques concurrently. The two techniques had a negligible mean difference and a 1.5% standard deviation in the one-dimensional shock zone. Within one interferometer delay time after a sudden Doppler shift, a SMV unencumbered by multimode-fiber dispersion exhibits two color beats. These beats have the same period as PDV beats-this interference occurs between the "recently" shifted and "formerly unshifted" paths within the interferometer. We believe that recognizing this identity between homodyne and heterodyne beats is novel in the shock-physics field. SMV includes the conveniences of optical fiber, while removing the time resolution limitations associated with the multimode delivery fiber.

The role of connexin36 gap junctions in modulating the hypnotic effects of isoflurane and propofol in mice.

Gap junction blockade is a possible mechanism by which general anaesthetic drugs cause unconsciousness. We measured the sensitivity of connexin36 knockout mice to the hypnotic effects of isoflurane and propofol. The experimental endpoint was recovery of the righting reflex of the anaesthetised animals during 0.2% step-reductions in isoflurane concentration, or following intraperitoneal injection of propofol (100 mg.kg(-1) ). Connexin36 knockout animals were more sensitive to the hypnotic effects of isoflurane than 'normal' wild-type animals. The half maximal effective concentration (EC50) for recovery of righting reflex was 0.37% for connexin36 knockout vs 0.49% for wild-type animals (p < 0.001). For propofol, connnexin36 knockout animals showed more rapid loss of righting reflex than wild-type animals (mean (SD) 2.8 (0.13) vs 3.8 (0.27) min); and young (< 60 days) connexin36 knockout animals remained anaesthetised for longer than young wild-type mice (47.2 (2.9) vs 30.5 (1.7) min; p < 0.00001). These findings suggest that the hypnotic effects of anaesthetic drugs may be moderately enhanced by gap junction blockade.

Toenail onychomycosis: an important global disease burden.

Onychomycosis is a fungal infection of the nail plate or nail bed. It does not usually cure itself and it can trigger more infectious lesions in other parts of the body. The reported prevalence of onychomycosis is increasing in Western countries, presumably due to lifestyle changes and the ageing of the population. Approximately 10% of the general population, 20% of the population aged>60 years, up to 50% of people aged>70 years and up to one-third of diabetic individuals have onychomycosis. Care should be taken for the accurate diagnosis and timely treatment of toenail onychomycosis to prevent complications. Current treatment options have relatively limited therapeutic success, particularly long-term. Oral medications are associated with high recurrence rates and treatment failure, and are not suitable for many cases due to potential adverse effects. Topical medications are recommended only for mild to moderate cases. The cost of therapies may also be prohibitive in some cases. In the light of these issues, more research is warranted for the investigation and development of more effective and economical options for the treatment and prophylaxis of toenail onychomycosis. In patient populations such as diabetic individuals, where onychomycosis can provoke lower extremity complications, professional podiatry care of toenails and feet should be encouraged.

Size and albedo of Kuiper belt object 55636 from a stellar occultation.

The Kuiper belt is a collection of small bodies (Kuiper belt objects, KBOs) that lie beyond the orbit of Neptune and which are believed to have formed contemporaneously with the planets. Their small size and great distance make them difficult to study. KBO 55636 (2002 TX(300)) is a member of the water-ice-rich Haumea KBO collisional family. The Haumea family are among the most highly reflective objects in the Solar System. Dynamical calculations indicate that the collision that created KBO 55636 occurred at least 1 Gyr ago. Here we report observations of a multi-chord stellar occultation by KBO 55636, which occurred on 9 October 2009 ut. We find that it has a mean radius of 143 +/- 5 km (assuming a circular solution). Allowing for possible elliptical shapes, we find a geometric albedo of in the V photometric band, which establishes that KBO 55636 is smaller than previously thought and that, like its parent body, it is highly reflective. The dynamical age implies either that KBO 55636 has an active resurfacing mechanism, or that fresh water-ice in the outer Solar System can persist for gigayear timescales.

Volatile organic compounds in runners near a roadway: increased blood levels after short-duration exercise.

OBJECTIVE: To determine if non-elite athletes undertaking short duration running exercise adjacent to a busy roadway experience increased blood levels of common pollutant volatile organic compounds (benzene, toluene, ethylbenzene and xylene (BTEX)). DESIGN AND SETTING: The study was observational in design. Participants (nine males/one female non-elite athletes) ran for 20 min, near a busy roadway along a 100 m defined course at their own pace. Blood levels of BTEX were determined both pre- and post-exercise by SPME-GC-MS. Environmental BTEX levels were determined by passive adsorption samplers. RESULTS: Subjects completed a mean (range) distance of 4.4 (3.4 to 5.2) km over 20 min (4.5 (3.8 to 5.9) min/km pace), with a mean (SD) exercise intensity of 93 (2.3)% HR(max), and mean (SD) ventilation significantly elevated compared with resting levels (86.2 (2.3) vs 8.7 (0.9) l/min; p<0.001). The mean (SD) environmental levels (time weighted average) were determined as 53.1 (4.2), 428 (83), and 80.0 (3.7) microg/m(3) for toluene, ethylbenzene and xylenes, respectively, while benzene was below the detectable limit due to the short exposure period. Significant increases in blood BTEX levels were observed in runners between pre- and postexercise for toluene (mean increase of 1.4 ng/ml; p=0.002), ethylbenzene (0.7 ng/ml; p=0.0003), m/p-xylene (2.0 ng/ml; p=0.004) and o-xylene (1.1 ng/ml; p=0.002), but no change was observed for benzene. CONCLUSIONS: Blood BTEX levels are increased during high-intensity exercise such as running undertaken in areas with BTEX pollution, even with a short duration of exercise. This may have health implications for runners who regularly exercise near roadways.

Norepinephrine content in the hypothalamus and medulla oblongata of ISIAH rats is regulated by several genetic loci.

Five genetic loci regulating epinephrine content in rat hypothalamus and two loci in the medulla oblongata were identified using polymorphic microsatellite DNA markers. Allele polymorphism of these loci determines the differences between norepinephrine levels in brain compartments of hypertensive ISIAH and normotensive WAG rats. The interactions between the detected epinephrine-regulating loci are additive.

Evaluation of repellent properties of volatile extracts from the Australian native plant Kunzea ambigua against Aedes aegypti (Diptera: Culcidae).

Kunzea ambigua (Smith) Druce (Myrtaceae) is an Australian native plant, commonly known as tick bush. The essential oil of the plant has been proposed as a potential mosquito repellent. Commercial K. ambigua oil was analyzed by gas chromatography-mass spectrometry (GC-MS) and its composition compared with that of oils from two individual K. ambigua plants and citronella oil. K. ambigua oils were studied for their repellency against Aedes aegypti L. Formulations of three different K. ambigua essential oils (30% vol:vol) were tested for repellency to mosquitoes using human volunteers. One oil was compared with citronella and N,N'-diethyl-3-methylbenzamide (deet) for repellency. Oil formulations were also tested for repellency with and without the addition of 5% vanillin. The formulation containing commercially produced K. ambigua oil had a mean complete protection time (CPT) of 49 +/- 24 (SD) min. All the K. ambigua formulations had comparable repellency to 40% citronella. However, the 60% citronella formulation showed higher repellency than the 40% K. ambigua formulation. The addition of 5% vanillin did not increase the repellency of K. ambigua oil. Both K. ambigua oil and citronella were significantly less repellent than deet. The K. ambigua essential oil formulations should not be advocated for use as repellents in regions prone to mosquito-borne disease.

Delayed effect of hypotensive drugs on blood pressure and structure of the myocardium in hypertensive ISIAH rats during chronic stress.

Administration of antihypertensive drugs alpha(1)-adrenoceptor antagonist and Ca(2+) channel blocker during early ontogeny had various delayed effects on blood pressure in ISIAH rats with inherited stress-induced arterial hypertension under resting conditions and chronic stress. The drugs did not prevent the development of myocardial hypertrophy. Chronic stress had little effect on myocardial structure in adult animals.

Randomised controlled trial of the treatment of pastern dermatitis with a formulation containing kunzea oil.

The efficacy of an ointment containing kunzea oil for the treatment of horses with localised acute or chronic pastern dermatitis was assessed. Thirty-seven horses were randomly allocated to treatment with an ointment containing either 20 per cent kunzea oil (test) or 2 per cent ketoconazole (control). Only 21 of the horses completed the study. The severity of the lesions was assessed before and after seven days of treatment. The kunzea oil formulation resulted in a significant decrease in the median total area of the lesions from 40 cm(2) (range 3 to 252 cm(2)) to 0 cm(2) (range 0 to 34 cm(2)), with complete resolution of the signs of pastern dermatitis in seven of 11 cases. The control formulation resulted in no significant change in the total area of the lesions, and the signs of pastern dermatitis resolved completely in only two of the 10 cases.

Suicide ideation among later elementary school-aged youth.

Suicide is extremely rare among persons under age 15 years old. Nationwide, it has been reported that 18% of students in grade 6 had thoughts of killing themselves. The Social Disintegration Model (SDM) summarizes intra-personal, interpersonal, peer network, physical and heath risk behaviour characteristics that may influence suicide ideation. As part of a larger study to test a family strengthening programme, 179 later elementary school children from two cities responded to 20 items about their participation in health risk behaviour. Sixteen youth indicated they had thought of killing themselves. Based on the SDM, these 16 youth were compared with the larger sample on measures of ways of coping; family communication, functioning and caring; school connectedness, pubertal development; and alcohol use and weapon carrying. Youth who responded positively to the 'thought of killing self' screening question, felt less connected to their school, used more internalizing behaviours and reported less cohesion, open communication, supervision and family caring than youth who answered no. Youth who thought of killing themselves may benefit from additional school support to feel more comfortable and connected at school. Community resources may help parents modify child-rearing behaviours. Building communication among parents and youth may prevent suicidal behaviour among young adolescents.

Chemoradiation for invasive cervical cancer in elderly patients: outcomes and morbidity.

Age may impact survival and treatment in cervical cancer patients. We sought to determine if treatment and survival were different in elderly patients and whether chemoradiation increased morbidity. We performed a retrospective chart review to identify patients treated with definitive radiation therapy at the University of Iowa Hospitals and Clinics between 1997 and 2001. Three hundred sixty-four patients had a new diagnosis of invasive cervical cancer, of which 150 patients were treated with radiation. We excluded patients treated postoperatively or with palliative intent, leaving 96 patients treated with definitive radiation therapy. Patients were divided into two age categories: elderly (>/=65) and nonelderly (<65). We compared these groups with respect to treatment received, morbidity, and survival. Sixty-nine (72%) women were less than 65 years old, and 27 (28%) women were greater than or equal to 65 years old. Chemoradiation was associated with decreased mortality (P < 0.01). The decrease in mortality did not differ between the two age cohorts (all causes: P = 0.66; cancer specific: P = 0.65), nor was there a difference in the complication rate due to chemoradiation (P = 0.70). Although elderly patients were more likely to be diagnosed with nonsquamous histologies (P < 0.01), their odds of receiving chemoradiation were 0.35 (95% CI: 0.13-0.90) times the odds for nonelderly. Elderly cervical cancer patients more often have nonsquamous histology and are likely to receive only radiation therapy compared to younger patients. Treatment with chemoradiation was associated with similar survival increases in both age cohorts. Complication rates between the two were similar. Chemoradiation should be considered in elderly patients with invasive cervical cancer.