Evidence for enemy release in invasive common dace Leuciscus leuciscus in Ireland: a helminth community survey and systematic review.

Invasive species lose parasites in the process of invasion and tend to be less parasitized than conspecifics in the native range and sympatric native species in the invasive range (enemy release). We evaluated enemy release in an invasive freshwater fish in Ireland, common dace Leuciscus leuciscus, using helminth parasite community surveys at the core and front of the invasive range of common dace. Furthermore, we undertook a systematic literature review of helminth infection in common dace across its native range in Great Britain and Europe and invasive range in Ireland. The helminth parasite community survey revealed that invasive common dace were infected with fewer helminth species at the invasion front than at the core. Four helminth taxa - Acanthocephala, Monogenea, Digenea and Nematoda - were present in dace at the invasion core compared to only a single helminth species (Pomphorhynchus tereticollis) at the front. The systematic review revealed that invasive common dace in Ireland hosted fewer species of helminths than common dace in the native range. We report a total of three helminth species in common dace in Ireland compared to 24 in Great Britain and 84 in Continental Europe. Our results support the hypotheses that invasive populations are less parasitized than native populations and that more recently established populations host fewer parasites. However, we demonstrate that invasive species may continue to experience release from parasites long after initial invasion.

Refolding of a membrane protein in a microfluidics reactor.

Membrane protein production for structural studies is often hindered by the formation of non-specific aggregates from which the protein has to be denatured and then refolded to a functional state. We developed a new approach, which uses microfluidics channels, to refold protein correctly in quantities sufficient for structural studies. Green fluorescent protein (GFP), a soluble protein, and bacteriorhodopsin (BR), a transmembrane protein, were used to demonstrate the efficiency of the process. Urea-denatured GFP refolded as the urea diffused away from the protein, forming in the channel a uniform fluorescent band when observed by confocal microscopy. Sodium dodecyl sulphate-denatured BR refolded within the channel on mixing with detergent-lipid mixed micelles. The refolding, monitored by absorbance spectroscopy, was found to be flow rate dependent. This potential of microfluidic reactors for screening protein-folding conditions and producing protein would be particularly amenable for high-throughput applications required in structural genomics.

Application of frequency-domain Fluorescence Lifetime Imaging Microscopy as a quantitative analytical tool for microfluidic devices.

We describe the application of wide-field frequency domain Fluorescence Lifetime Imaging Microscopy (FLIM) to imaging in microfluidic devices. FLIM is performed using low cost, intensity modulated Light Emitting Diodes (LEDs) for illumination. The use of lifetime imaging for quantitative analysis within such devices is demonstrated by mapping the molecular diffusion of iodide ions across a microchannel.

Chemical arthrodesis of the distal tarsal joints using sodium monoiodoacetate in 104 horses.

OBJECTIVE: To evaluate chemical arthrodesis using sodium monoiodoacetate for treatment of degenerative joint disease of the tarsometatarsal and distal intertarsal joints. DESIGN: Retrospective clinical study. METHOD: Horses were diagnosed with degenerative joint disease of one or more of the tarsometatarsal or distal intertarsal joints based on history, lameness examination, radiographic findings and, in some cases, response to intra-articular anaesthesia or medication. Intra-articular injections of sodium monoiodoacetate were performed using 23 gauge needles in the sedated, standing horse. Positive contrast arthrography of the distal intertarsal joint was performed in all horses to evaluate needle placement and the presence or absence of communication with other synovial structures. The mean intra-articular dose of sodium monoiodoacetate was 192 mg. Horses were subject to a graded exercise program commencing 7 to 10 days after treatment. Where possible, follow up lameness examination and radiography was performed at 3, 6, 12 and 24 months after treatment. RESULTS: At 3, 6, 12 and 24 months after treatment, respectively, 0/57, 14/55, 41/50, and 29/34 of horses were sound. At 3, 6, 12 and 24 months after treatment, respectively, 5/55, 24/38, 26/30 and 18/18 of horses had radiographic evidence of ankylosis of treated joints. Post injection pain was marked in 6.7% of horses and significant complications requiring further treatment occurred in 3.8% of horses. CONCLUSIONS: Chemical arthrodesis using sodium monoiodoacetate was an effective treatment method for degenerative joint disease of the distal tarsal joints. The technique was performed in the sedated standing horse and required minimal equipment. Results were comparable to those achieved following surgical arthrodesis. The risk of significant complications was minimised through good technique using an appropriate injection volume and concentration.

Characterization of wheezing phenotypes in the first 10 years of life.

BACKGROUND: Childhood wheezing illnesses are characterized into different phenotypes. However, severity of the disease associated with these phenotypes has not been extensively studied. OBJECTIVES: To determine characteristics of childhood wheezing phenotypes in the first decade of life using health outcomes plus measurements of atopy, lung function and bronchial hyper-responsiveness. METHODS: A whole population birth cohort (n = 1456) was prospectively studied to examine the natural history of childhood wheezing. Children were seen at 1, 2, 4 and 10 years for questionnaire completion and prospectively collected data used to define wheezing phenotypes. Assessment was made of adverse health outcomes plus spirometry, bronchial hyper-responsiveness, serum IgE measurement at 10 years and skin test sensitization at both 4 and 10 years for wheezing phenotypes. RESULTS: Phenotypic analysis identified that 37% early life wheezers (symptom onset by age 4 years) still wheezed at 10 years. These persistent wheezers showed significantly more physician-diagnosed asthma in early life (P < 0.005 at 2 years) than early transient wheezers (wheezing transiently with onset by age 4 years). Overall they experienced greater multiple hospital admissions (P = 0.024), specialist referral (P = 0.009) and use of inhaled (P < 0.001) and oral steroids (P < 0.001) than early transient wheezers. They also demonstrated enhanced bronchial hyper-responsiveness compared with early transient wheezers (P < 0.001). However, both groups of early life wheezers showed impairment of baseline lung function at 10 years in comparison with non-wheezers: FEV1 (P < 0.029) and FEV1/FVC ratio (P < 0.001) with persistent wheeze and PEF (P = 0.036) with early transient wheeze. Late-onset wheezers (onset from 5 years onwards) had similar BHR to persistent wheezers but maintained normal lung function at age 10 and had lower cumulative prevalence of adverse health outcomes than persistent wheezers. CONCLUSIONS: Persistent wheezing with early childhood onset is associated with substantial morbidity in the first decade of life in association with high levels of atopy, bronchial hyper-responsiveness and impaired lung function at 10 years of age. Late-onset wheezing in the first decade of life could harbour potential for similarly significant disease subsequently.

Primary prevention of asthma and atopy during childhood by allergen avoidance in infancy: a randomised controlled study.

BACKGROUND: Recent increases in the prevalence of asthma and atopy emphasise the need for devising effective methods for primary prevention in children at high risk of atopy. METHOD: A birth cohort of genetically at risk infants was recruited in 1990 to a randomised controlled study. Allergen avoidance measures were instituted from birth in the prophylactic group (n=58). Infants were either breast fed with mother on a low allergen diet or given an extensively hydrolysed formula. Exposure to house dust mite was reduced by the use of an acaricide and mattress covers. The control group (n=62) followed standard advice as normally given by the health visitors. At age 8, all 120 children completed a questionnaire and 110 (92%) had all assessments (skin prick test, spirometry, and bronchial challenges). RESULTS: In the prophylactic group eight children (13.8%) had current wheeze compared with 17 (27.4%) in the control group (p=0.08). Respective figures were eight (13.8%) and 20 (32.3%) for nocturnal cough (p=0.02) and 11 of 55 (20.0%) and 29 of 62 (46.8%) for atopy (p=0.003). After adjusting for confounding variables, the prophylactic group was found to be at a significantly reduced risk for current wheeze (odds ratio (OR) 0.26 (95% confidence interval (CI) 0.07 to 0.96)), nocturnal cough (OR 0.22 (95% CI 0.06 to 0.83)), asthma as defined by wheeze and bronchial hyperresponsiveness (OR 0.11 (95% CI 0.01 to 1.02)), and atopy (OR 0.21 (95% CI 0.07 to 0.62)). CONCLUSION: Strict allergen avoidance in infancy in high risk children reduces the development of allergic sensitisation to house dust mite. Our results suggest that this may prevent some cases of childhood asthma.

Delta9-tetrahydrocannabinol stimulates palatable food intake in Lewis rats: effects of peripheral and central administration.

To further study effects of delta9-tetrahydrocannabinol (THC) on food intake, male Lewis rats were maintained on rat chow and, on testing days, presented with chocolate cake batter (CCB) for 4h in addition to chow. Chow intake was not affected by THC administration in either experiment. In experiment 1 (n = 13) THC was administered intraperitoneally, and low doses produced increases in CCB intake for up to 1 h while the highest dose significantly decreased CCB intake over this same time period. In experiment 2 (n = 10) THC was injected intracerebroventricularly. Doses of 2.5, 10 and 25 microg significantly increased CCB intake for up to 1 h while stimulatory effects following 5 microg lasted up to 2h. Overall THC produced short-term increases in palatable food intake following both peripheral and central administration. Intraperitoneal administration resulted in an "inverted U" dose-response curve at all time points, while all central doses resulted in increased intake early in the time course and the hyperphagic effects were of greater duration than those following peripheral administration.

Influence of smoking on asthmatic symptoms and allergen sensitisation in early childhood.

BACKGROUND: Apart from heredity, several early life environmental factors are implicated in the development of childhood asthma. Maternal smoking is believed to increase asthmatic symptoms but its influence on the development of allergen sensitisation is debatable. STUDY DESIGN: A whole population birth cohort was reviewed at ages 1, 2, and 4 years. Of 1218 children seen at 4 years, 981 (80.5%) were skin prick tested with a battery of common food and aeroallergens. Smoking history was recorded at birth and updated at each follow up and its impact on the development of asthma and allergen sensitisation in the children was assessed. RESULTS: Two hundred and fifty mothers smoked during pregnancy (20.5%) and 307 (25.2%) after childbirth. Maternal smoking in pregnancy was associated with low birth weight (mean (SD): 3.3 (0.5) v. 3.5 (0.5) kg; p<0.001). Smoking mothers were more often from lower social classes (31.8% v. 16%, p<0. 001) and they breast fed their babies for a shorter duration (8.5 (11.4) v. 16.6 (15.2) weeks; p<0.001). The difference in breast feeding duration was partly due to a higher proportion of smoking mothers who never breast fed their babies. Although at age 2 years asthmatic symptoms were associated with exposure to maternal tobacco smoke (odds ratio 2.2, 95% confidence interval 1.5 to 3.4; p<0.001), this association was lost by 4 years. However, maternal smoking was a significant risk factor in a subgroup of children with asthmatic symptoms but negative skin prick test. Maternal smoking did not increase allergen sensitisation at age 4 years. No effect of paternal smoking on asthma was observed in the children.

Egg allergy in infancy predicts respiratory allergic disease by 4 years of age.

Sensitization to hen's egg early in life has been proposed as a predictor for respiratory allergic disease during childhood. However, symptomatic egg allergy in infancy has not been studied in this context. In 1989, a cohort of consecutive births was recruited. Data on family history of atopy and environmental factors were collected. At 4 years of age, 1,218 children were seen of whom 981 were skin-prick tested with a range of food and aero-allergens. Of the 1,218 children, 29 (2.4%) had suffered symptomatic egg allergy (20 during infancy). Egg allergy in infancy was associated with increased respiratory (asthma, rhinitis) allergic disease (odds ratio [OR] 5.0, 95% confidence intervals [CI] 1.1-22.3; p < 0.05) at 4 years of age, with a positive predictive value (PPV) of 55.0%. The addition of infantile eczema to egg allergy increased the PPV to 80% whereas the addition of family history of atopy had no effect. Egg allergy also increased aero-allergen sensitization (OR 6.1, CI 1.1-37.5; PPV 61.1%; p < 0.05). As a predictor for respiratory allergic disease and aeroallergen sensitization, it carried a high specificity but poor sensitivity. Hence, egg allergy in infancy, especially when coexisting with eczema, increases respiratory allergic symptoms and aero-allergen sensitization in early childhood.

Elevated cord serum IgE increases the risk of aeroallergen sensitization without increasing respiratory allergic symptoms in early childhood.

BACKGROUND: Increasing prevalence of allergic disorders has focused attention on primary prevention. There is a need to improve the accuracy of early-life predictors of atopy so that the at-risk population can be accurately defined and preventive measures instituted. OBJECTIVE: The predictive capacity of elevated cord IgE, with or without family history of atopy, to allergic symptoms and skin prick test (SPT) sensitization is evaluated in a birth cohort followed up prospectively for 4 years. METHODS: A birth cohort of 1456 consecutively born children was recruited in 1989. Data were collected on family history of atopy and cord serum total IgE (cord IgE) was measured. Of these, 1218 children were seen in the clinic at 4 years to determine the development of symptoms and signs of allergic disease and 981 were skin tested to a range of common food and aeroallergens. RESULTS: Of 1218 children reviewed at age 4 years, 218 (17.8%) had symptoms of respiratory allergy and, of those skin tested (n = 981), 192 (19.6%) reacted positively. Twice as many children with elevated cord IgE (>/= 0.5 kU/L) at birth became sensitized to aeroallergens by age 4 years (34.8% vs 17.3%, P < 0. 001). Positive predictive value (PPV) of elevated cord IgE for the development of aeroallergen sensitization was better than that of family history of atopy (34.8 vs 22.6%). Combining paternal atopy with elevated cord IgE substantially increased the predictive capacity (PPV 77.8%). Cord IgE levels did not correlate with clinical asthma or rhinitis at age 4 years and PPV for allergic respiratory symptoms remained poor at all cutoffs. CONCLUSION: Cord IgE is better than family history for predicting atopy as defined by allergen sensitization and this predictive value can be further increased by combining cord IgE with paternal atopy.

The prevalence of and risk factors for atopy in early childhood: a whole population birth cohort study.

OBJECTIVES: A birth cohort was followed-up to age 4 years to record the development of allergic disorders and to study the influence of genetic and environmental factors. METHODS: Information on family history and environmental factors was obtained at birth, and serum cord IgE was measured. At age 4 years, 1218 children were reviewed. RESULTS: By age 4 years, 27% of the children had symptoms of allergic disease. Period prevalence of asthma increased from 8.7% in infancy to 14.9% at 4 years. Family history of atopy was the single most important risk factor for atopy in children. Sibling atopy was a stronger predictor of clinical disease than maternal or paternal atopy, whereas paternal atopy, male sex, and high cord IgE were significant for the development of allergen sensitization. Children of asthmatic mothers were three times more likely to have asthma (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.6-5.8) and rhinitis (OR: 2.9, CI: 1.1-7.4). Formula feeding before 3 months of age predisposed to asthma at age 4 years (OR: 1.8, CI: 1.2-2.6). The effect of maternal smoking on childhood wheeze seen at 1 and 2 years was lost by age 4, except for a subgroup with negative skin test responses (nonatopic asthma). Less than half (46%) of the infantile wheezers were still wheezing at 4 years of age. CONCLUSION: Family history of atopy remains the most important risk factor for atopy in children, but other markers can be identified with a potential for intervention at an early age.

Relapse and rehospitalization during maintenance treatment of schizophrenia. The effects of dose reduction and family treatment.

BACKGROUND: Previous studies have examined dose reduction and family treatment in schizophrenia, but none has examined their interaction. This study assessed the impact of dose reduction of antipsychotic medication and family treatment on relapse and rehospitalization during maintenance treatment. METHODS: Subjects were 313 male and female outpatients at 5 centers with a DSM-III-R diagnosis of schizophrenia or schizoaffective disorder. In a 3 x 2 design, subjects were randomized to 1 of 3 medication strategies using fluphenazine decanoate under double-blind conditions: continuous moderate dose (standard) (12.5-50 mg every 2 weeks); continuous low dose (2.5-10 mg every 2 weeks); or targeted, early intervention (fluphenazine only when symptomatic). Subjects also were randomized to 1 of 2 family treatment strategies (supportive or applied). Supportive family management involved monthly group meetings. The more intensive applied family management involved monthly group meetings and home visits where communication and problem-solving skills were taught. Patients and families were treated and assessed for 2 years. RESULTS: Both continuous low-dose and targeted treatment increased use of rescue medication and relapse; only targeted treatment increased rehospitalization. This pattern was consistent across both family treatments; there were no differences between family treatments. CONCLUSIONS: These findings reaffirm the value of antipsychotic medication in preventing relapse and rehospitalization. The absence of family treatment differences may be because both conditions engaged families.

Sensitization to Alternaria and Cladosporium by the age of 4 years.

Of 1218 children born on the Isle of Wight in 1989/90, and followed for atopy at age 4 years, 981 were skin-prick tested with a battery of allergens. Of these 61 (6%) reacted positively to Alternaria alternata and Cladosporium herbarum (47 to Alternaria, 21 to Cladosporium and seven to both). Twenty-four (39%) were asymptomatic (latent atopy) of which 12 had a single positive reaction either to Alternaria or Cladosporium. Asthma was the most common disease in children sensitized to moulds. Alternaria sensitization correlated positively with clinical diagnosis of asthma (P < 0.01), eczema (P < 0.001) and rhinitis (P < 0.05). Likewise, Cladosporium sensitivity correlated with a diagnoses of asthma, eczema and rhinitis (all P < 0.05). Age of the house correlated with reported damp and lack of central heating (both P < 0.001), but not with sensitization to moulds. An association between the presence of damp or age of the house and mould allergy was confounded by 21 children moving house in the first 4 years. Exposure to pets, passive tobacco smoking and season of birth had no bearing on mould sensitivity. At 4 years of age Alternaria and Cladosporium were the third most common causes of sensitization, i.e. after house dust mite and grass pollen.

No correlation between nigral degeneration and striatal plaques in Alzheimer's disease.

Although Alzheimer's disease may involve both the substantia nigra and the striatum, there is little information concerning the relationship between the resulting abnormalities in these reciprocally interconnected regions of the brain. We have examined the correlation between plaque density in the striatum and counts of neurons and neurofibrillary tangles in the pars compacta of the substantia nigra, in 12 cases of "pure" Alzheimer's disease (i.e. without clinical or neuropathological evidence of Parkinson's or cortical Lewy body disease) and 11 normal controls. Diffuse plaques in the striatum and neurofibrillary tangles in the substantia nigra were consistent findings in all of the Alzheimer brains. However, quantitation did not reveal a statistically significant correlation between the density of striatal plaques and the numbers of either neurofibrillary tangles or neurons in the substantia nigra. Although the mean number of neurons in the substantia nigra of Alzheimer brains was lower than that in controls, the difference did not reach statistical significance. We suggest that previous assessments of substantial loss of nigral neurons in Alzheimer's disease may have been skewed by the inclusion of cases with coexistent cortical Lewy bodies.

Family treatment for schizophrenia : the design and research application of therapist training models.

The NIMH Treatment Strategies in Schizophrenia (TSS) collaborative study group investigated the efficacy of antisychotic drug maintenance strategies involving reduced medication exposure in interaction with applied and supportive family management for the long-term treatment of schizophrenia. Therapy was provided at five centers by 25 clinicians who did not participate in the development of the therapies. They were trained by two of the authors, I.R.H.F and C.W.M, in applied family management, a homebased treatment derived from the behavioral family therapy developed by them. Clinicians' characteristics, selection, and training methods, as well as patient rehospitalization rates, are reported for the two family management conditions. The TSS study represents a bridge between the development of a novel therapy and its dissemination in general clinical practice.

Maintenance treatment of schizophrenia: a review of dose reduction and family treatment strategies.

Maintenance treatment in schizophrenia requires the integration of both medication and psychosocial treatment interventions for maximum effect. We review the recent evidence for strategies drawn from both domains. For the use of anti-psychotic medication we focus on studies of dose reduction using two strategies that differ in assumptions regarding the action of medication. They are: continuous low-dose and targeted, early intervention or intermittent treatment. For psychosocial interventions we focus on studies of family treatment. Regarding dose reduction, we conclude that both strategies are feasible but the targeted strategy incurs higher relapse and rehospitalization rates. Regarding family treatment, we conclude that family treatment provides benefits beyond other psychosocial interventions or usual care, but that there is no evidence for differences in efficacy among family treatments.

First-episode psychosis: Part I. Editors' introduction.

Until recently, there has been a conspicuous lack of studies regarding the earliest phases of psychotic illness, with most research on schizophrenia and related disorders focusing on chronically ill patients. Currently, however, a number of investigators have turned their attention toward this topic, exploring the conceptual issues involved in defining the onset of psychosis, using case registers and population-based samples to do crucial epidemiologic studies on the course of schizophrenia, and developing mechanisms for identifying patients with first-episode psychosis and entering them into active research protocols. The issue of the Schizophrenia Bulletin is devoted to articles representing this full range of conceptual and empirical work on first-episode psychosis. The ultimate goal is for researchers working in this area to develop a network to enhance the sharing of concepts and data, with the eventual possibility of developing combined data bases and collaborative studies.

Research on first-episode psychosis: report on a National Institute of Mental Health Workshop.

The need to focus increased research on patients experiencing their first episode of psychosis was emphasized in A National Plan for Schizophrenia Research. To develop strategies for enhancing research in this area, a National Institute of Mental Health Workshop on First-Episode Psychosis was held in 1991. The topics discussed at that workshop are summarized, with key issues including the following: (1) the need for better operational definitions of onset, end of an episode, and relapse of psychosis; (2) careful consideration of inclusion and exclusion criteria related to age, gender, prior treatment, comorbid substance abuse, and similar issues; (3) the challenge of finding patients never exposed to neuroleptics and the value of entering first-episode patients into standardized treatment protocols; (4) the design of followup studies; (5) strategies to increase the pool of applicants; and (6) approaches for increasing power through data sharing and collaboration between groups.