Deconstructing the evolutionary complexity between rust fungi (Pucciniales) and their plant hosts.

The rust fungi (Pucciniales) are the most speciose natural group of plant pathogens, members of which possess the most complex lifecycles in Fungi. How natural selection works on the Pucciniales has been the subject of several hypotheses in mycology. This study uses molecular age estimation using sequence data from multiple loci, and cophylogeny reconciliation analyses to test hypotheses regarding how the aecial and telial stages in the lifecycle of rust fungi may have differentially impacted their diversification. Molecular age estimates show that the timing of diversification in the Pucciniales correlates with the diversification of their gymnosperm and angiosperm hosts. Host reconciliation analyses suggest that systematic relationships of hosts from the aecial stage of the Pucciniales lifecycle better reflect the systematic relationships among the Pucciniales. The results demonstrate the relative importance of this stage on the overall evolution of the Pucciniales and supports hypotheses made by Leppik over half a century ago. This study represents the first evaluation of how different life stages in the Pucciniales shape the evolution of these fungi.

Periaqueductal Grey EP3 Receptors Facilitate Spinal Nociception in Arthritic Secondary Hypersensitivity.

UNLABELLED: Descending controls on spinal nociceptive processing play a pivotal role in shaping the pain experience after tissue injury. Secondary hypersensitivity develops within undamaged tissue adjacent and distant to damaged sites. Spinal neuronal pools innervating regions of secondary hypersensitivity are dominated by descending facilitation that amplifies spinal inputs from unsensitized peripheral nociceptors. Cyclooxygenase-prostaglandin (PG) E2 signaling within the ventrolateral periaqueductal gray (vlPAG) is pronociceptive in naive and acutely inflamed animals, but its contributions in more prolonged inflammation and, importantly, secondary hypersensitivity remain unknown. In naive rats, PG EP3 receptor (EP3R) antagonism in vlPAG modulated noxious withdrawal reflex (EMG) thresholds to preferential C-nociceptor, but not A-nociceptor, activation and raised thermal withdrawal thresholds in awake animals. In rats with inflammatory arthritis, secondary mechanical and thermal hypersensitivity of the hindpaw developed and was associated with spinal sensitization to A-nociceptor inputs alone. In arthritic rats, blockade of vlPAG EP3R raised EMG thresholds to C-nociceptor activation in the area of secondary hypersensitivity to a degree equivalent to that evoked by the same manipulation in naive rats. Importantly, vlPAG EP3R blockade also affected responses to A-nociceptor activation, but only in arthritic animals. We conclude that vlPAG EP3R activity exerts an equivalent facilitation on the spinal processing of C-nociceptor inputs in naive and arthritic animals, but gains in effects on spinal A-nociceptor processing from a region of secondary hypersensitivity. Therefore, the spinal sensitization to A-nociceptor inputs associated with secondary hypersensitivity is likely to be at least partly dependent on descending prostanergic facilitation from the vlPAG. SIGNIFICANCE STATEMENT: After tissue damage, sensitivity to painful stimulation develops in undamaged areas (secondary hypersensitivity). This is found in many painful conditions, particularly arthritis. The periaqueductal gray (PAG) is an important center that controls spinal nociceptive processing, on which secondary hypersensitivity depends. Prostaglandins (PGs) are mediators of inflammation with pronociceptive actions within the PAG under normal conditions. We find that secondary hindpaw hypersensitivity in arthritic rats results from spinal sensitization to peripheral A-nociceptor inputs. In the PAG of arthritic, but not naive, rats, there is enhanced control of spinal A-nociceptor processing through PG EP3 receptors. The descending facilitatory actions of intra-PAG PGs play a direct and central role in the maintenance of inflammatory secondary hypersensitivity, particularly relating to the processing of A-fiber nociceptive information.

Lower leg muscle density is independently associated with fall status in community-dwelling older adults.

UNLABELLED: Muscle density is a risk factor for fractures in older adults; however, its association with falls is not well described. After adjusting for biologically relevant confounding factors, a unit decrease in muscle density was associated with a 17 % increase in odds of reporting a fall, independent of functional mobility. INTRODUCTION: Falls are the leading cause of injury, disability, and fractures in older adults. Low muscle density (i.e., caused by muscle adiposity) and functional mobility have been identified as risk factors for incident disability and fractures in older adults; however, it is not known if these are also independently associated with falls. The purpose of this study was to explore the associations of muscle density and functional mobility with fall status. METHODS: Cross-sectional observational study of 183 men and women aged 60-98 years. Descriptive data, including a 12-month fall recall, Timed Up and Go (TUG) test performance, lower leg muscle area, and density. Odds ratio (OR) of being a faller were calculated, adjusted for age, sex, body mass index, general health status, diabetes, and comorbidities. RESULTS: Every mg/cm(3) increase in muscle density (mean 70.2, SD 2.6 mg/cm(3)) independently reduced the odds of being a faller by 19 % (OR 0.81 [95 % CI 0.67 to 0.97]), and every 1 s longer TUG test time (mean 9.8, SD 2.6 s) independently increased the odds by 17 % (OR 1.17 [95 % CI 1.01 to 1.37]). When both muscle density and TUG test time were included in the same model, only age (OR 0.93 [95 % CI 0.87 to 0.99]) and muscle density (OR 0.83 [95 % CI 0.69 to 0.99]) were independently associated with fall status. CONCLUSIONS: Muscle density was associated with fall status, independent of functional mobility. Muscle density may compliment functional mobility tests as a biometric outcome for assessing fall risk in well-functioning older adults.

Lower-extremity muscle atrophy and fat infiltration after chronic spinal cord injury.

BACKGROUND: Atrophy and fatty-infiltration of lower-extremity muscle after spinal cord injury (SCI) predisposes individuals to metabolic disease and related mortality. OBJECTIVES: To determine the magnitude of atrophy and fatty-infiltration of lower-extremity muscles and related factors in a group of individuals with chronic SCI and diverse impairment. METHODS: Muscle cross-sectional area and density were calculated from peripheral quantitative computed tomography scans of the 66% site of the calf of 70 participants with chronic SCI [50 male, mean age 49 (standard deviation 12) years, C2-T12, AIS A-D] and matched controls. Regression models for muscle area and density were formed using 16 potential correlates selected a priori. RESULTS: Participants with motor-complete SCI had ≈ 32% lower muscle area, and ≈ 43% lower muscle density values relative to controls. Participants with motor-incomplete SCI had muscle area and density values that were both ≈ 14% lower than controls. Body mass (+), tetraplegia (+), motor function (+), spasticity (+), vigorous physical activity (+), wheelchair use (-), age (-), and waist circumference (-) were associated with muscle size and/or density in best-fit regression models. CONCLUSIONS: There are modifiable factors related to muscle size, body composition, and activity level that may offer therapeutic targets for preserving metabolic health after chronic SCI.

The Rose Rust Fungus, Phragmidium tuberculatum, is Widespread in the Americas: First Reports from California, Oregon, Massachusetts, and Honduras.

The rust fungus Phragmidium tuberculatum Jul. Müll. is a common pathogen on Rosa spp., on which all life cycle stages are formed. Symptoms occur in spring and may include distorted stems, yellow spots on the upper leaf surface, and a bright orange spore mass formed on the abaxial leaf surface. In late summer, sori become speckled with black as fascicles of teliospores develop. The current known distribution of P. tuberculatum is mostly limited to Europe with some occurrence in Asia and into Australasia (2). There is some documented occurrence in North America (Alaska, Connecticut, and Canada [2]), where most rose rust disease is attributed to P. mucronatum (Pers.) Schltdl. This study used a combination of molecular and morphological analyses on newly collected material from across North America (California: BPI877978, PURN7783; Oregon: BPI877980; Massachusetts: BPI877977; and Quebec: BPI877979) and herbarium material from South and Central America (Honduras: BPI864186; and Argentina: BPI843677; both previously identified as P. mucronatum) to document a much broader distribution of P. tuberculatum. Collectively, teliospores from these collections are 4 to 6 celled, dark to black-brown, warted, elongated to cylindrical, 64.7 to 92.4 µm in length by 23.1 to 39.3 µm in width (average 77.6 × 30.0 µm) (30 teliospores from 2 leaves), with 2 to 3 pores/cell and a pronounced hyaline apiculus 4.6 to 18.5 µm long (average 8.3 µm). P. tuberculatum is similar morphologically to P. mucronatum, but sensu Gäumann (3) differs in having wider (30 to 36 µm) and longer (65 to 110 µm) teliospores with an average of 6 to 8 cells/spore. However, the two are easily distinguished by DNA analyses (4). The 28S sequences were amplified using the protocols described in Aime (1) and compared phylogenetically to 28S sequences available in the GenBank database for P. tuberculatum, P. mucronatum, and other Phragmidium spp. (4). In a maximum likelihood analysis, all isolates formed a 99% bootstrap supported clade with P. tuberculatum sequences from Germany, and shared 100% sequence identity with JF907675 P. tuberculatum. In contrast, comparison with HQ421646 P. mucronatum produced only 92% identity (e.g., 836/911 bp for PURN7783). This information indicates that P. tuberculatum is likely to be widespread in the Americas but simply misidentified as P. mucronatum, as was found to be the case for the two herbarium specimens sampled. Detailed examination of historical herbarium material may help to pinpoint how long the fungus has been present and the current extent of its distribution. The rose rust fungus is not considered to be a problem economically, but its spread within North America may be an indicator of commercial practices that serve as a vector for other diseases on ornamental plants. Voucher specimens have been deposited in the U.S. National Fungus Collections (BPI) and Arthur Fungarium (PUR); voucher sequences are deposited in GenBank (Accession Nos. KJ841917 to 23). References: (1) M. C. Aime. Mycoscience 47:112, 2006. (2) J. F. Arthur. Manual of the rusts in United States and Canada. Purdue Research Foundation, 1934. (3) E. Gäumann. Die Rostpilze Mitteleuropas mit besonderer Berücksichtigung der Schweiz. Büchler, Bern, 1959. (4) C. M. Ritz et al. Mycol. Res. 109:603, 2005.

First Report of the White Pine Blister Rust Fungus, Cronartium ribicola, on Ribes odoratum in Indiana.

Cronartium ribicola J. C. Fisch., causal agent of white pine blister rust (WPBR), is one of the most damaging pathogens of five-needle pines, forming aecial states on the trunk and branches and causing cankering, topkill, and branch dieback. Infection can predispose hosts to attack by other pests such as bark beetles, and can result in host mortality. Various species of Ribes, Pedicularis, and Castilleja are alternate hosts on which C. ribicola forms its uredinial and telial states during the mid-summer to fall. In an effort to mitigate the damage caused by white pine blister rust, the planting of ornamental species of Ribes, such as R. occidentalis, is prohibited in 14 states. Indiana currently has no restrictions on the planting of Ribes spp. Since 2010, a Cronartium sp. has been observed producing uredinia and telia on R. odoratum 'Crandall' H.L. Wendl. leaves in an urban environment in West Lafayette, Indiana. Symptoms include yellow-orange lesions on the leaf upper surface with uredinia on the underside. These persist from late summer until leaf drop. Telia were collected in 2011 to establish the identity of the causal agent using morphological and molecular analyses. Morphological comparisons between this specimen and other Cronartium species were made using Arthur (2). Filiform telial columns ranged from 0.5 to 1.5 mm in length. Teliospores were cylindrical to sub-ventricose, truncate on either end with one end generally tapering more than the other, and measured 9.0 to 18.6 × 37.2 to 60.0 µm (average 11.9 × 47.4 µm from 30 spores across 4 leaves). These teliospore measurements overlap those of C. ribicola and C. occidentale, but are more consistent with C. ribicola, in which the spores are wider and longer (8 to 12 × 30 to 60 µm) than in C. occidentale (9 to 10 × 27 to 56 µm). For molecular analyses, two nuclear ribosomal loci were sequenced: the internal transcribed spacer regions 1, 2, and 5.8S (ITS) and the 5' end of the large subunit (28S) (1). The ITS sequence was 665 bp long (KF387533) and the 28S was 892 bp (KC876675). These sequences were queried to GenBank using a BLASTn search. The 28S shared 99% identity (891/892 bp) and the ITS shared 100% identity (663/663 bp) to other published C. ribicola sequences with no close matches to any other species with either locus. Both morphological and molecular methods indicate this species to be C ribicola, making this a first report of white pine blister rust on R. odoratum in Indiana. This fungus has been observed previously on R. odoratum in the northeastern United States (Connecticut, Massachusetts, Rhode Island, Vermont, and New Hampshire), the Rockies (Colorado), northwestern United States (Washington), and Canada (3). In Indiana, C. ribicola has also been reported on R. cysnobati. There are no other reports of this fungus on any other host within the state. However, the aecial host, Pinus strobus, does grow within the state, and within West Lafayette. To our knowledge, WPBR has only been observed (not reported) once in Indiana in the past 30 years (Paul Pecknold, personal communication). Further monitoring of C. ribicola hosts is needed in Indiana to determine the extent of the disease. The specimen has been vouchered in the Arthur Herbarium (PUR N6734). References: (1) M. C. Aime. Mycoscience 47:112. 2006. (2) J. F. Arthur. Manual of the Rusts in United States and Canada. Purdue Research Foundation, 1934. (3) D. F. Farr and A. Y. Rossman. Fungal Databases Systematic Mycology and Microbiology Laboratory, ARS, USDA. Retrieved from http://nt.ars-grin.gov/fungaldatabases/ April 23, 2013.

Evaluating the role of the diagnostic radiographer in identifying child safeguarding concerns: A knowledge, attitude and practice survey approach.

INTRODUCTION: Child safeguarding and the appropriate identification of suspected victims represents a global phenomenon. Diagnostic imaging is acknowledged as a contributory diagnostic service but the role of the radiographer in the identification and escalation process is less well understood. METHOD: A Knowledge, Attitude and Practice (KAP) survey was constructed to evaluate knowledge base in the context of the patient-radiographer interaction, the shaping of attitude towards child safeguarding and attitudes held towards their role plus the actual practical experiences of managing child safeguarding concerns. RESULTS: Respondents demonstrated a inconsistent knowledge base with respect to physical, social and radiographic signs and symptoms of child safeguarding concern. A positive attitude towards the role of the radiographer in child safeguarding was demonstrated but one that was shaped more by experience than pre-registration education. Assessment of concerns was chiefly influenced by clinical history and appreciation of aetiology. Practically, radiographers have infrequent involvement with the identification and escalation of concerns. Whilst some statistically significant relationships between responses and demographics did exist, these were either sporadic or argued to be a result of natural variation. CONCLUSION: Assessment of physical and social signs of child safeguarding concern are argued to be becoming more challenging. Radiological signs continue to be visible to radiographers but with increasing use of other imaging modalities these signs are becoming more varied in nature and are providing new challenges. Radiographers are capable of escalation when required to do so. IMPLICATIONS FOR PRACTICE: To maximise the contribution of the profession, education needs to account for imaging modality worked with, in combination with an understanding of related aetiology. Previously existing concerns with respect to escalating processes are no longer in evidence and radiographers are both willing and able to contribute to that process.

Dose-response effects of sotalol on cardiovascular function in conscious, freely moving cynomolgus monkeys.

BACKGROUND AND PURPOSE: The non-selective beta-adrenoceptor antagonist, D,L-sotalol (sotalol) is commonly employed as a positive control during preclinical cardiovascular safety pharmacology testing, mainly because of its ability to prolong QT interval duration. However, no information appears in the literature, except in abstract form, regarding the dose-response effects of sotalol in unanesthetized monkeys. The current study was conducted to determine the dose- and plasma-response effects of orally administered sotalol on cardiovascular function in conscious non-human primates. EXPERIMENTAL APPROACH: Male cynomolgus monkeys were implanted with telemetry devices and the effects of sotalol hydrochloride (5, 10 and 30 mg kg(-1) of body weight, p.o.) on arterial blood pressure, heart rate, body temperature and electrocardiogram waveform were continuously monitored for 6 h after dosing. Blood was sampled for the measurement of plasma concentrations of sotalol. KEY RESULTS: Sotalol dose dependently decreased heart rate and prolonged RR, PR, QT and corrected QT intervals, while having little or no effects on the QRS complex, arterial pressure or body temperature, over the dose range tested. When the data were related to plasma concentrations of sotalol, it was clear that the cardiovascular effects occurred in a similar pattern and to a comparable degree as those reported in human studies. CONCLUSIONS AND IMPLICATIONS: The current study helps demonstrate the validity of utilizing telemetry-instrumented non-human primates for the cardiovascular safety pharmacology assessment of drugs prior to first-in-human testing, and its findings may serve as a reference source for the dose- and plasma-response effects of orally administered sotalol in conscious monkeys.

Maze model to study spatial learning and memory in freely moving monkeys.

Many types of mazes have been used in cognitive brain research and data obtained from those experiments, especially those from rodents' studies, support the idea that the hippocampus is related to spatial learning and memory. But the results from non-human primates researches regarding the role of the hippocampus in spatial learning and memory are controversial and inconsistent with those obtained in rodents. This might be due to the differences of the methods used in non-human primates and rodents. Several kinds of maze models including two-dimensional computerized visual maze models and three-dimensional maze models have been developed for non-human primates, but they all have some defects. Therefore, development of a maze model for non-human primates that is comparable with those used in rodents is necessary to solve the controversy. This paper describes a large-scale, three-dimensional outdoor maze model for non-human primates which can be used to study spatial learning and memory. Monkeys learn to use the maze quickly compared with two-dimensional computerized visual mazes. It has many advantages which could make up the limits of the existing three-dimensional mazes in non-human primates, and can be comparable with radial arm mazes used in rodents. Based on the results, we believe that the new maze model will be valuable in many research areas, especially in studies involving spatial learning and memory in freely moving monkeys.

Factors influencing the occurrence of multicentric and 'recurrent' Warthin's tumour: a cross sectional study.

The multicentric nature of Warthin's tumour has been well recognised, though the factors predicting its occurrence and its influence on management remain speculative. In this cross sectional study, the authors analysed the presentation, management and outcome of solitary and multicentric Warthin's tumour, treated in the maxillofacial unit and investigated factors that could influence the occurrence of multicentric and recurrent tumours. Warthin's tumour was found in 24% (150/628) of patients presenting with parotid neoplasms and multicentric tumours were found in 13% (21/ 161) of parotidectomy specimens. Age, sex, side, site and smoking history were not predictors of multicentricity (P>0.40). Clinical examination (19%), imaging investigations (28%) and intra-operative palpation (33%) were poor at detecting multicentric tumours. Superficial parotidectomy was the most commonly performed operation. The recurrence rate was 0% in the solitary and 10% in the multicentric tumour group. Intra-operative rupture was not uncommon (11%), but was not associated with tumour recurrence (P= or >0.999). Incomplete excision (P=0.007) and multicentricity (P=0.026) were predictors of recurrence.

Multiple synchronous and metachronous neoplasms of the parotid gland: the Chichester experience.

Parotid neoplasms are usually solitary and multiple tumours occurring in an individual are uncommon. The incidence and implications of multiple synchronous and metachronous tumours remains relatively unknown. We reviewed the case notes of 606 patients who had parotidectomies for neoplastic lesions over a 30 year period and identified 30 patients (5%) with multiple primary tumours. There were 24 patients with synchronous tumours and 6 with metachronous tumours. Sixteen of the synchronous tumours (67%) were ipsilateral, whereas all six metachronous tumours were contralateral. Preoperative examination was effective at detecting bilateral tumours but poor at detecting multiple ipsilateral tumours. Multiple tumours were likely to be of the same histology (n=24, 80%) and Warthin's was by far the most common multiple tumour. Ipsilateral tumours of differing histological types and identical tumours other than Wartin's were uncommon. All but one patient had superficial parotidectomies and there were no recurrences.

Transmasseteric antero-parotid approach for open reduction and internal fixation of condylar fractures.

The morbidity that results from surgical approaches to the condylar neck, and the time-consuming nature of the operation inhibits many surgeons from using open reduction and internal fixation for the treatment of condylar fractures. The many approaches that have been described stand testimony to the disadvantages of the individual techniques. The most common problems are limited access and injury to the facial nerve. We describe the transmasseteric antero-parotid (TMAP) technique, which offers swift access to the condylar neck while substantially reducing the risk to the facial nerve and eliminating the complications associated with transparotid approaches.

Another use of the Foley catheter: retraction for operations on the floor of mouth and ventral aspect of the tongue.

A Foley catheter that is passed through the nose and sutured to the tip of the tongue can be used to facilitate retraction for operations on lesions on the ventral aspect of the tongue and the floor of the mouth. It provides excellent access and is simple, inexpensive, atraumatic, minimises frustration, reduces the operating time, and eliminates some of the difficulties associated with the use of metal retractors.

Effects of pergolide treatment on in vivo hydroxyl free radical formation during infusion of 6-hydroxydopamine in rat striatum.

This study focused on the early neurochemical events involved in 6-hydroxydopamine (6-OHDA) neurotoxicity and the putative neuroprotective effects of pergolide. 6-OHDA in 0.1% ascorbic acid/saline was delivered into rat striatum by means of microdialysis and 2,3-dihydroxybenzoic acid (2,3-DHBA) was measured as an index of hydroxyl free radical formation using salicylate trapping. Infusion of 6-OHDA (2-20 mM) via the dialysis probe for 15 min was associated with an immediate and striking increase in the extracellular levels of 2,3-DHBA and dopamine, and this effect was dose-dependent. An infusion of 10 mM 6-OHDA, equivalent to a direct injection of approximately 4 microgram free base, resulted in dopamine overflow with a maximum approx. 200-fold above the baseline. This massive overflow of toxic amounts of dopamine, much greater than expected of reuptake inhibition, seems to be the earliest response of nigrostriatal neurones to 6-OHDA. In rats treated with pergolide mesylate (7 days 0.5 mg/kg/day, i.p.), the average amount of 2, 3-DHBA associated with 6-OHDA striatal infusion was significantly smaller than that in controls. This suggests that pergolide treatment leads to an increased ability of striatal tissue to quench hydroxyl radical formation in vivo.

Manipulation of operant responding for an ethanol-paired conditioned stimulus in the rat by pharmacological alteration of the serotonergic system.

It is becoming increasingly clear that environmental stimuli play a critical role in the maintenance of drug taking behaviour. This has led to investigations into the neural mechanisms by which environmental stimuli can come to control behaviour using paradigms such as conditioned reinforcement. The majority of this work has involved the use of food-paired conditioned stimulus rodent paradigms. Relatively few studies have attempted to investigate the neuropharmacology of behaviour maintained by presentation of a stimulus paired with ethanol drinking. Several lines of research support an important role for brain serotonin (5-HT) neurotransmitter systems in the control of alcohol drinking behaviour. The aim of the present study was, initially, to establish a procedure in which rats respond for an ethanol-paired conditioned stimulus, and second, to study the effects of a range of serotonergic compounds previously shown to be effective in reducing oral ethanol self-administration, on responding for this conditioned stimulus. Results showed that the 5-HT releaser d-fenfluramine, the selective serotonin reuptake inhibitor fluoxetine, the 5-HT1A receptor agonist 8-hydroxy-2[di-n-propylamino]tetralin, the partial 5-HT1A receptor agonist buspirone, and the 5-HT1B/5-HT2C receptor agonist 1-(3-trifluoromethylphenyl)piperazine, but not the 5-HT2A/5-HT2C receptor agonist 1-(2,5-dimethoxy-4-iodophenylaminopropane)-2, selectively reduced responding on a lever leading to presentation of an ethanol paired conditioned stimulus. In addition the non-specific D1/D2 dopamine receptor antagonist haloperidol was active in this paradigm. Results are consistent with involvement of the dopaminergic and 5-HT systems, in particular activation of 5-HT1A and 5-HT1B receptor subtypes, in mediation of the conditioned or secondary reinforcing properties of ethanol.

Azoles for allergic bronchopulmonary aspergillosis associated with asthma.

BACKGROUND: Allergic Broncho-pulmonary Aspergillosis is hypersensitivity to the fungus Aspergillus fumigatus that complicates patients with asthma and cystic fibrosis. The mainstay of treatment for ABPA remains oral corticosteroids, though this does not completely prevent exacerbations and may not prevent the decline in lung function. OBJECTIVES: The purpose of this review was to determine the efficacy of azoles in the treatment of Allergic Broncho-pulmonary Aspergillosis. SEARCH STRATEGY: The Cochrane Airways Group Asthma register was searched using the terms: (allergic bronchopulmonary aspergillosis OR aspergillosis OR allergic pulmonary aspergillosis OR allergic fungal and disease OR allergic mycotic and disease) AND (azole OR triazole OR itraconazole OR ketoconazole). SELECTION CRITERIA: All controlled trials that assessed the effect of azole antifungal agents compared to placebo or other standard therapy for ABPA were reviewed. Patients with cystic fibrosis were not included. DATA COLLECTION AND ANALYSIS: All identified trials were independently reviewed by both reviewers & all data collected. Trial quality was scored by the Cochrane assessment of allocation concealment & the Jadad scale of methodological quality. MAIN RESULTS: Twelve trials were identified, but only three were prospective, randomised and controlled. One demonstrated a reduction in immunological markers of disease activity and symptom scores using ketoconazole 400 mg daily for 12 month. There was no significant improvement in lung function. The other two examined the use of itraconazole for 16 weeks. In one there was a reduction in sputum eosinophils by 35% compared to 19% with placebo (p<0.01). In the same trial, the number of exacerbations requiring oral corticosteroids was 0.4 per patient with itraconazole compared with 1.3 per patient with placebo (p<0.03). Meta analysis of data from both trials showed that itraconazole treated patients were more likely to have decline in serum IgE over 25% or more (Odds Ratio 3.3; 95% confidence intervals 1.3, 8.2). REVIEWER'S CONCLUSIONS: Itraconazole modifies the immunologic activation associated with ABPA and improves clinical outcome in ABPA at least over the period of 16 weeks.

Azoles for allergic bronchopulmonary aspergillosis.

BACKGROUND: Allergic Broncho-pulmonary Aspergillosis (ABPA) is hypersensitivity to the fungus Aspergillus Fumigatus that complicates patients with asthma and cystic fibrosis. The condition usually results in an increase in symptoms, a greater reliance on corticosteroids to control the disease process and may lead to a progressive decline in lung function. The mainstay of treatment for ABPA remains oral corticosteroids, though this does not completely prevent exacerbations and may not prevent the decline in lung function. OBJECTIVES: The purpose of this review is to determine the efficacy of azoles in the treatment of ABPA SEARCH STRATEGY: An initial search was carried out using the Cochrane Airways Group Asthma RCT register. The register was searched using the following terms: (asthma or wheeze) and (allergic bronchopulmonary aspergillosis or aspergillosis or allergic pulmonary aspergillosis or allergic fungal and disease or allergic mycotic and disease) and (azole or triazole or itraconazole or ketoconazole). SELECTION CRITERIA: All controlled trials that assessed the effect of azole antifungal agents compared to placebo or other standard, for any duration or dose regimen in subjects with ABPA of any age or severity were reviewed. Studies in languages other than English were included. DATA COLLECTION AND ANALYSIS: All identified trials were independently reviewed by both reviewers & all data collected. Trial quality was scored by the Cochrane assessment of allocation concealment & the Jadad scale of methodological quality. MAIN RESULTS: A total of 11 trials were identified concerning the use of azoles in ABPA. Only two prospective controlled trials were identified. The first trial examined the use of Ketoconazole 400 mg daily for 12 months and demonstrated a reduction in immunological markers of disease activity and symptom scores, there was no significant improvement in lung function. The other trial examined the use of itraconazole for 16 weeks. This demonstrated a reduction in corticosteroid usage, an improvement in immunological markers, an improvement in pulmonary function and exercise tolerance. This study was only available as an abstract and limited details were available. REVIEWER'S CONCLUSIONS: There is insufficient information available to recommend the use of azole anti-fungal agents in the routine treatment of patients with ABPA.

Can some physical therapy and manual techniques generate potentially osteogenic levels of strain within mammalian bone?

BACKGROUND AND PURPOSE: Although physical therapy techniques are used to alleviate pain and stiffness in joint injuries, whether these methods are capable of affecting bone is unknown. For example, can these techniques potentially influence bone formation or resorption? To begin exploring this possibility, this study investigated the ability of 4 manual techniques to generate levels of compressive strains that presumably can stimulate bone metabolism. SUBJECTS: Six 3,4 metacarpals from three 3-year-old Merino ewes were used. METHODS: A rosette strain gauge was implanted onto the dorsomedial cortex of each ovine 3,4 metacarpal. Four different manual procedures were applied on 2 occasions on each metacarpal in vivo and ex vivo. Mean peak principal compressive strains were calculated for each technique. RESULTS: Levered bending produced greater mean peak compressive strains than almost all other manual procedures tested in vivo or ex vivo. CONCLUSION AND DISCUSSION: Manual levered bending created levels of compressive strain similar in magnitude to those created by mechanical devices used in previous animal experiments to induce new bone formation (osteogenesis). This animal model appears to be suitable for investigating the effects of manually applied procedures on bone and may establish whether manual techniques can stimulate bone formation.

The 5-HT1A receptor agonist 8-OH-DPAT reduces ethanol intake and maintained behavior in female Sprague-Dawley rats.

Agents affecting serotonergic (5-hydroxytryptamine, 5-HT) function influence ethanol consumption in rats and primates. In the present study female Sprague-Dawley rats were trained to orally self-administer 8% ethanol (v/v) in a large operant chamber in a 60-min test period by a prandial drinking technique. The number of response, ethanol reinforcers (dipper deliveries), and ethanol consumption (g/kg) were measured following administration of the 5-HT1 A agonist 8-OH-DPAT (0.001 1.0 mg/kg, ip) 30 min prior to testing. Locomotor activity (LMA) was also measured to assess activity changes induced by 8-OH-DPAT. 8-OH-DPAT selectively reduced ethanol ingestion from 17.1 +/- 3.2 dipper deliveries under vehicle conditions to 6.6 +/- 3 at a dose of 0.1 mg/kg. Higher doses of 8-OH-DPAT (0.5 and 1.0 mg/kg) significantly reduced both ethanol ingestion and LMA. Lower doses of 0.001-0.01 mg/kg of 8-OH-DPAT were without effect on ethanol intake and maintained behavior. These results demonstrate that, under the present experimental conditions, the 5-HT1A receptor agonist 8-OH-DPAT reduced ethanol self-administration in the rat, and support a role for 5-HT1A receptors in the mediation of ethanol reinforcement.

An investigation into the effects of 5-HT agonists and receptor antagonists on ethanol self-administration in the rat.

Pharmacological manipulation leading to altered 5-HT function has been widely demonstrated to reduce ethanol intake in free choice tests. The aim of the present study was to examine the effects of a range of compounds known to influence 5-HT neurotransmission, including selective 5-HT receptor agonists and antagonists, on ethanol ingestion and maintained behaviour in an operant self-administration paradigm. Female Sprague-Dawley rats were trained to respond for 8% ethanol (v/v) in a 60-min test by a previously described technique. The number of responses and ethanol reinforcers (dipper deliveries), ethanol consumption (g/kg of body weight), and locomotor activity (LMA) were measured following administration of 5-HT agonists (5-HT, d-fenfluramine, fluoxetine, buspirone, TFMPP, and DOI) and antagonists (metergoline, ritanserin, and ondansetron) 30 min prior to testing. d-Fenfluramine, fluoxetine, buspirone, TFMPP, and DOI all produced a reduction in ethanol ingestion and maintained behaviour at doses that failed to reduce LMA. Conversely, metergoline and ritanserin only reduced ethanol self-administration at doses that concomitantly reduced LMA. 5-HT and ondansetron were without effect on any measure. These results demonstrate that, under the present experimental conditions, activation of central 5-HT1A, 5-HT1B, and 5-HT2 receptors reduced ethanol intake and reinforced behaviour in an operant paradigm.