Britton

The International Union against Tuberculosis and Lung Disease (IUATLD) Bronchial Symptoms Questionnaire (1984) was developed for use in studies of asthma and its reliability measured in an earlier survey in England. The association of the symptoms elicited by this questionnaire to bronchial response to histamine has also been described. This paper presents the results of studies of the questionnaire in four clinical centres in Europe. The reliability of the questionnaire and its ability to predict the bronchial response to histamine were compared for English, Finnish, French and German translations of the questionnaire in samples of diagnosed asthmatics and controls in Nottingham, Berlin, Helsinki and Paris. The answers to questions showed good repeatability, especially in Finland and Germany, particularly those questions on asthma and wheeze. The most sensitive symptom for predicting hyperresponsiveness was the question on wheeze, the most specific questions were those on waking at night with shortness of breath (Paris and Nottingham) and morning tightness (Helsinki and Berlin). This study shows that the IUATLD (1984) questionnaire may provide useful, valid and comparable data even in translation but these studies will need to be repeated in representative samples before such a possibility is accepted as fully demonstrated.

Clinical & Experimental AllergyVolume 30, Issue 5 p. 615-627 The role of diet in the aetiology of asthma Fogarty, Fogarty Division of Respiratory Medicine, University of Nottingham, City Hospital, Nottingham, UKSearch for more papers by this author Britton, Britton Division of Respiratory Medicine, University of Nottingham, City Hospital, Nottingham, UKSearch for more papers by this author Fogarty, Fogarty Division of Respiratory Medicine, University of Nottingham, City Hospital, Nottingham, UKSearch for more papers by this author Britton, Britton Division of Respiratory Medicine, University of Nottingham, City Hospital, Nottingham, UKSearch for more papers by this author First published: 24 December 2001 https://doi.org/10.1046/j.1365-2222.2000.00766.xCitations: 105 Britton Division of Respiratory Medicine, University of Nottingham, City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume30, Issue5May 2000Pages 615-627 RelatedInformation

Objective To determine the association between the β 2 ‐adrenoceptor polymorphisms at amino acids 16 and 27 and markers of allergic disease and asthma per se in a random adult population, and to determine the degree of linkage disequilibrium existing between polymorphisms at amino acid positions 16, 27, 164 and nucleic acid residue 523. Methods We measured serum IgE, skin‐prick test positivity, atopy, bronchial hyperreactivity, wheeze and asthma (self‐reported and doctor‐diagnosed), and determined β 2 ‐adrenoceptor genotype by allele specific oligonucleotide hybridization, in 630 adults aged between 18 and 70, selected from the electoral role in a local health authority in Nottingham. Results Homozygotes for the Glycine 16 polymorphism had a significantly higher incidence of atopy (χ 2 = 6.44 (Pearson's), P = 0.04). We also observed a significant association between the Glycine 16 allele and atopy (χ 2 = 4.13 (Pearson's), P = 0.04), when we assumed the Glycine 16 allele to operate in a dominant mode. No other significant associations between β 2 ‐adrenoceptor polymorphisms and markers of allergic disease and asthma per se were observed. Marked linkage disequilibrium exists between the β 2 ‐adrenoceptor polymorphisms at amino acid 16 and 27 (D = 0.38, χ 2 P < 0.0001), and between the β 2 ‐adrenoceptor polymorphisms at amino acid 27 and nucleic acid residue 523 (C‐A) (D = 0.36, χ 2 P < 0.0001). Conclusion There is no consistent association between β 2 ‐adrenoceptor polymorphisms and the risk of developing allergic disease or asthma per se in this adult sample. Marked linkage disequilibrium exists between the amino acid 16 and 27 polymorphisms, and also between the amino acid 27 polymorphism and the nucleic acid residue 523 (C‐A) polymorphism. This polymorphism accounts for the Ban 1 RFLP previously described at the β 2 ‐adrenoceptor locus on chromosome 5q 31.

Tumour necrosis factor (TNF) is a pivotal cytokine in the inflammation underlying asthma. The TNF gene is located in the polymorphic HLA class 3 region on chromosome 6p. Several polymorphisms in this region have been described and associated with alteration of TNF secretion in vitro.In this study we tested the hypothesis that two such polymorphisms, lymphotoxin alpha NcoI B*1 and -308 TNF2 may be components of the genetic predisposition to asthma.Five hundred and fifty-six random individuals were studied, comprising approximately equal numbers of asthmatic subjects, with or without atopy, and a nonatopic nonasthmatic control group. In addition, 355 subjects (172 asthmatics) from 60 multiplex families were typed at the LTalpha NcoI locus.There was an association between allele two of the -308 TNF polymorphism and bronchial hyperreactivity (OR 2.12, 95% CI 1.04-4.32, P = 0.036). However, there was no association with LTalpha NcoI alleles. To determine whether this was influenced by linkage disequilibrium within the MHC, 91 subjects with bronchial hyperreactivity and 85 control subjects were typed for class 2 and 3 alleles. Following identification of the extended TNF2 haplotype, we found no independent association of these alleles with BHR.We conclude that the -308 TNF2 promoter polymorphism may form a component of the genetic predisposition to BHR in asthma.

The development of more effective antituberculosis vaccines would assist in the control of the global problem of infection with Mycobacterium tuberculosis. One recent vaccination strategy is immunization with DNA plasmids encoding individual microbial genes. Using the genes for the M. tuberculosis-secreted proteins, MPT64 (23 000 MW) and Ag85B (30 000 MW) as candidate antigens, we previously prepared DNA vaccines and demonstrated their ability to stimulate T-cell responses and confer protection in a mouse model of aerosol tuberculosis (TB). The protective efficacy of the DNA vaccines was less than that promoted by the current vaccine Mycobacterium bovis bacille Calmette-Guèrin (BCG). To improve the immunogenicity and protective efficacy of these mycobacterial vectors, co-immunization of a plasmid expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) was investigated. Intramuscular immunization with DNA expressing MPT64 or Ag85B and GM-CSF enhanced the antigen-specific cellular immune response, with increased proliferative response and production of interferon-gamma (IFN-gamma). The titre of antimycobacterial protein immunoglobulin G (IgG) antibodies was unchanged. Mice immunized with DNA vaccines showed reduced pulmonary bacterial load following an aerosol challenge of M. tuberculosis, but codelivery of the plasmid expressing GM-CSF did not increase the protective effect. Therefore, despite modifying the cellular immune response to DNA vaccines, GM-CSF does not improve their protective efficacy at the peak of infection after an aerosol challenge with 100 c.f.u. of M. tuberculosis.

Background It has recently been suggested that measles infection may reduce the risk of atopy. Objective To study the independent effect of measles infection and measles vaccination on the occurrence of hay fever in a British national birth cohort. Methods In over 6000 children born in 1970, details of immunizations and childhood diseases were collected by parental interviews at ages 5, 10 and 16 years, and hay fever within the past year at age 16 years. Results In univariate analysis, hay fever was less common in those contracting measles infection than in those not infected (OR 0.86, 95% CI 0.76–0.96), and more common in those given measles vaccination than in those not vaccinated (OR 1.16, 95% CI 1.03–1.31). However, these effects were strongly confounded by birth order, which was closely associated with the likelihood of receiving measles vaccination and with the risk of hay fever. A strong interaction between the effects of measles vaccination and infection, and birth order was found, such that in those with many older sibling contacts, hay fever was significantly and independently reduced in relation to both measles infection and measles vaccination relative to those who were neither infected nor vaccinated. Conclusions Both measles infection and measles vaccination in childhood appear to reduce the risk of hay fever in children with multiple older sibling contacts. Differential exposure or response to the measles virus may explain the effect of birth order on the occurrence of allergic disease.

T he overall aim of the NHS R&D Health Technology Assessment (HTA) programme is to ensure that high-quality research information on the costs, effectiveness and broader impact of health technologies is produced in the most efficient way for those who use, manage

Bronchial responsiveness to histamine or methacholine provides a useful objective measure for epidemiological studies of airways disease, but most people in a community population do not have a 20% fall in forced expiratory volume in one second (FEV1) with the highest dose administered. Histamine challenge data were analysed to compare the repeatability. Normality and separation of symptom groups of the early dose-response slope with provocative dose producing a 20% fall in FEV1 (PD20). Tests were continued until a 20% fall in FEV1 occurred, or 4 mumol had been given. Data were available for 510 randomly selected subjects, and for an additional 283 with wheeze. A repeat test was obtained in 104 individuals. PD20 was estimated by curve fitting, with extrapolation to 8 mumol. Least-squares slope of percentage decline in FEV1 on histamine dose was calculated, using all the measured points and two-point slope as the fall from the post-saline measurement to the maximum cumulative dose divided by the maximum dose. Log transformation of PD20 and shifted reciprocal transformations of slope produced constant variance. Over all subjects the three measures had similar repeatability; in subjects with PD20 > 8 mumol the intraclass correlation for two-point slope was only 0.26, but was 0.66 for least-squares slope. Neither measure of slope was normally distributed, but the distribution of log(PD20) was consistent with a censored normal distribution. In conclusion, least-squares slope is preferable to two-point slope for epidemiological studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical & Experimental AllergyVolume 28, Issue S1 p. 2-7 Symptoms and objective measures to define the asthma phenotype Britton, Britton Division of Respiratory Medicine, City Hospital, Nottingham NG5 1PB, UKSearch for more papers by this author Britton, Britton Division of Respiratory Medicine, City Hospital, Nottingham NG5 1PB, UKSearch for more papers by this author First published: 04 January 2002 https://doi.org/10.1046/j.1365-2222.1998.0280s1002.xCitations: 15Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume28, IssueS1April 1998Pages 2-7 RelatedInformation

Classical models of the evolution of sex typically assume that an asexual lineage, once derived, is reproductively separate from the sexual lineage from which it was derived. However, many asexuals, including hermaphrodite plants, produce male gametes capable of fertilising the eggs of co‐existing sexuals, giving rise to sexual and asexual progeny. This male function of asexuals may be poor, and it has been proposed that this could favour sexuality and adversely affect the successful establishment of asexual lineages. We show that things are more complicated than this; the effect is frequency‐dependent and poor male function may sometimes favour asexuality. In a spatially distributed population of flowering plants, it can prevent the successful invasion of either reproductive mode by the other via long‐range dispersal. Consequently invasions must be driven by short‐range dispersal, and are therefore extremely slow. Thus poor male function favours long‐term co‐existence of sexuals and asexuals. When coupled with the superior ability of asexuals to colonise virgin territory after an Ice Age, it may explain current ecological distribution patterns.

While phantom limb pain is a well-recognized phenomenon, clinical experience has suggested that the augmentation of phantom limb pain with visceral stimulation is an issue for many military personnel with amputation (visceral stimulation being the sensation of the bowel or bladder either filling or evacuating). However, the prevalence of this phenomenon is not known. The aim of this study was to investigate the prevalence of the alteration in phantom limb pain and the effect that visceral stimulation has on phantom limb pain intensity. A cross-sectional study of 75 military personnel who have lost one or both lower limbs completed a questionnaire to assess the prevalence of the alteration of phantom limb pain with visceral stimulation. Included in the questionnaire was a pain visual analog scale (VAS) graded from 0 to 10. Patients recorded the presence and intensity of phantom limb pain. They also recorded whether and how this pain altered with a need to micturate or micturition, and/or a need to defecate or defecation, again using a pain VAS. Time since amputation, level of amputation, and medications were also recorded. Patients reported a phantom limb pain prevalence of 85% with a mean VAS of 3.6. In all, 56% of patients reported a change in the severity of phantom limb pain with visceral stimuli. The mean increase in VAS for visceral stimulation was 2.5 +/- 1.6 for bladder stimulation and 2.9 +/- 2.0 for bowel stimulation. Of the patients questioned, 65% reported an improvement in symptoms over time. VAS scores were highest in the subgroup less than 6 mo postamputation. An increase in phantom limb pain with visceral stimulation is a common problem for military personnel with amputation.

Background Both genetic and environmental factors are thought to contribute to specific IgE responses, however, the relative contribution of each in the responses to individual ryegrass pollen allergens is largely unknown even though some responses to allergens have been linked to certain HLA complexes. Objective Using a large group of monozygotic and dizygotic twins, this study was designed to investigate the IgE binding profiles of individual ryegrass pollen ( Lolium perenne ) components to assess the relative contribution of genetic and environmental factors in determining IgE responses to specific allergens. Methods Ryegrass pollen proteins were separated by electrophoresis and immunoblotted with sera from 191 pairs of twins where at least one sibling had a SPT > 2 mm to perennial ryegrass. Concordance levels for individual ryegrass pollen components were compared between monozygotic and dizygotic twins in a subset group where both twins had SPT > 3 mm to perennial ryegrass. Results Immunoblotting revealed 23 individual IgE‐binding components from ryegrass pollen. Although there was a significantly greater proportion of monozygotic twins with SPT wheals greater than 3 mm when compared with the dizygotic twins, the mean case‐wise concordance for the immunoblot components was similar for both groups of twins. The mean case‐wise concordance when at least four pairs of sera were involved was 44% for the MZ twins ( n = 11 components) and 45% for the DZ twins ( n = 12 components). We found no significant differences in concordance levels for any of the 23 individual components including allergens previously associated with HLA. Conclusion Evidence for genetic control of allergen‐specific IgE responses in a large population sample of twins to individual ryegrass allergens is limited, indicating that the IgE responses to specific ryegrass pollen allergens are determined largely by environmental factors.

Although the prevalence of allergic disease appears to be increasing in most parts of the world [ 1–3], there are still important differences in the prevalence and pattern of disease both between and within developed and developing countries [ 4]. Studies in Africa, for example, have found a generally lower prevalence of self-reported asthma symptoms [ 4–6] exercise-induced bronchospasm [ 7], and allergic rhinoconjunctivitis [ 6] relative to the developed world, especially in rural compared with urban areas [ 5, 8–10]. In addition to this generally lower prevalence of allergic disease, immunoglobulin (Ig) E levels in African populations tend to be high [ 11–15], and levels in nonasthmatics tend to be higher than in asthmatics. Since asthma, bronchial hyperreactivity and allergic disease tend to be associated with high IgE levels in the developed world [ 16–18], this apparent paradox calls for a reappraisal of the role of IgE in allergy in these populations. One hypothesis is that the high levels of IgE in African populations are caused by parasitic infestation, and that this in turn somehow reduces the risk of allergic disease. In this issue of Clinical and Experimental Allergy, Selassie et al. provide some new evidence relating to this hypothesis [ 19]. Intestinal parasites are potent stimulators of both parasite-specific IgE, which is important in the host immune response to parasite [ 20, 21], and polyclonal or non-specific IgE. Parasite specific IgE attaches to high-affinity Fc receptors on mast cells, and neighbouring specific immunoglobulins cross-link and trigger mast cell degranulation. This process mediates an antiparasite response via the release of pro-inflammatory cytokines. The same mechanism is involved in the pathogenesis of asthma and other allergic disease in which immune responses are triggered by allergen-specific IgE [ 17]. Since the immune responses involved in dealing with both parasites and allergy appear to be similar, it is plausible that parasitosis and allergy are somehow interrelated. The nature of this relationship has been extensively reviewed [ 22–24] but is still not understood. From experimental data [ 23, 25] it has been postulated that saturation of IgE receptors by the Fc fragment of parasite-induced non-specific IgE will block the cross-linking of allergen-specific IgE on the surface of mast cells and therefore prevent their degranulation and the subsequent allergic response. Thus parasite infestation may protect against allergy whilst, by the same token, the parasite-killing response is likely to be similarly inhibited. It has been postulated that the ability to generate this polyclonal response has evolved in the parasite because it helps to evade host immunity [ 24]. This latter theory is supported by work in Ascaris-endemic areas of Venezuela where Hagel et al. found that high total IgE was a marker of increased risk of re-infection after anthelmintic treatment [ 21]. Other studies have reached similar conclusions [ 20, 26]. This hypothesis, that current parasitic infection can protect against development and exacerbation of allergic disease, has been proposed to explain much of the available epidemiological evidence, but has not yet been definitively explored. Some studies provide evidence in support of this hypothesis, including a descriptive study of asthma in Kenya [ 27] which found that only 9% of stools from asthmatic patients showed parasite infestation compared with 26% of a control group. Unusual evidence was also reported by Turton [ 28], who found that his hay fever improved markedly after three separate self-infections with hookworm (Necator americanus). He also demonstrated that his specific antiparasite IgE level increased threefold during the 13-month period in which the infections occurred, but his total IgE did not increase in relation to pre-infection levels. These findings, though based on the experience of a single individual, suggest that parasite-specific IgE was blocking the allergic response. Further evidence comes from surveys in The Gambia [ 12] and Rhodesia [ 11], which both found higher levels of IgE in rural areas, in association with lower rates of asthma. They attributed the differences in IgE levels to differences in parasitosis in the rural areas, but did not determine whether these subjects were carrying intestinal parasites. The importance of this omission is demonstrated by a study in Nigeria where lower levels of IgE were observed in asthmatics, but with no difference in stool parasite counts between cases and controls [ 13]. Similar findings in Tanzanian school-children [ 14] also do not support the parasite-protective hypothesis. There is rather more evidence that parasitic infestation, as opposed to protecting against allergic disease, actually increases the risk. Lynch and colleagues [ 29] studied asthmatic children in Venezuelan slums and found that their asthma control improved significantly after anthelmintic treatment. Dold et al. studied school children from the former East and West Germany [ 30], looking at clinical evidence of allergic disease and immunological markers of parasitic infection. In a longitudinal study, in which a cohort of children was surveyed twice 3 years apart, they observed an increase in the prevalence of allergic rhinitis in children who became seropositive to Ascaris IgE. They also found a higher frequency of allergen-specific IgE in those who were Ascaris-seropositive at either survey, and that a positive Ascaris IgE result was a stronger risk factor for allergic sensitization to inhalant allergens than a family history of allergic disease. Another possibility in the ‘allergy-parasite’ story is that the atopic state may confer protection from parasitic infestation, a selective advantage that may account for the evolutionary persistence of an otherwise apparently negative trait. Further studies from Ascaris-endemic areas of Venezuela compared the parasite burden of children from an area known to have a high prevalence of atopic disease, with those from an area of similar socioeconomic status where there was a lower prevalence of atopy [ 26]. They found the intensity of parasitic infection was considerably lower in the atopic children, who had higher levels of specific anti-Ascaris IgE, emphasizing the importance of the specific antiparasite IgE in the protective immune response. A French paediatric outpatient population study [ 31] found the prevalence of intestinal parasitosis to be similar in atopic subjects and nonatopic controls, but observed that the atopic children experienced far less gastrointestinal symptoms than nonatopics. This study therefore suggests that the atopic phenotype may somehow downregulate the host systemic response to parasites, or simply result in lower parasite loads. In the study published in this issue [ 19], Selassie et al. compare two groups of urban adult outpatients attending a teaching hospital in Gondar, Ethiopia. The cases were patients with recurrent episodes of wheezy breathlessness, in whose case notes was recorded either a diagnosis, or treatment for, asthma. The controls were selected from other outpatients who had no recorded history of asthma or wheezy breathlessness and were attending the same hospital for non-respiratory conditions. The diagnosis of asthma was supported in this study by objective measurement of airway hyperresponsiveness, which was found in 81% of cases and 4% of controls, and although not formally matched, the groups appear similar in terms of age and sex. The authors found the total IgE levels to be high but not significantly different in cases and controls. There were, however, higher levels of Ascaris- and Necator-specific IgE antibodies in the controls than among the asthmatics, suggesting a protective effect of parasites against asthma. Like so many others, however, this study did not measure intestinal parasite burden, so we cannot determine whether the current parasitic load was responsible for this effect. The other significant finding in this study was the positive correlation between sensitivity to house dust mite antigen and a diagnosis of asthma. Raised levels of specific IgE antibodies to Der p 1 were found in 93% of asthmatics compared with 48% of controls, supporting previous findings in urban African environments [ 5, 32, 33]. The authors conclude that since there was no relationship between specific antiparasite IgE and the Der p 1 IgE levels, the ‘protective effect’ of parasite infection on asthma must be mediated by an effect independent of sensitization to common aeroallergens. This is inconsistent with previous theories that the parasite IgE mast cell saturation effect acts by blocking sensitization to subsequent environmental allergens [ 24]. The relationship between allergen sensitization and asthma is not straightforward, however, [ 4, 5], and appears to be dependent upon environmental factors. The Ethiopian study by Yemaneberhan et al. [ 5] found that skin prick test reactivity to Dermatophagoides pteronyssinus was positively correlated with wheeze in the urban environment, but appeared to be protective in the rural areas. A study comparing asthma and atopy in Australia and Nigeria [ 4] found that the prevalence of atopy was similar in the two countries, but there was significantly less reported wheeze and persistent cough in Nigeria, implying a much weaker relationship between asthma and atopy in the developing country. Interestingly, in Kenyan school children [ 15] the association of high IgE and exercise-induced bronchospasm (EIB) differed between the urban and rural children. In the urban area, raised IgE levels were correlated with EIB, whereas in the rural area, there was a non-significant trend towards an inverse association between IgE and EIB. This all suggests that other factors, probably related to the level of ‘urbanization’, account for the expression of allergic disease in those who are allergen-sensitized. By studying a group of outpatients, Selassie et al. will inevitably be susceptible to selection bias and possible confounding. Given the terrain and poor communications in Ethiopia, it may be expected that those who attend the hospital will be predominantly from urban areas, or will be the more affluent, or those who place a greater sense of priority on their health. As the data are not adjusted for urban–rural residence, they have to assume the relationship between atopy and asthma within their study population is constant. This may reduce the sensitivity of their study for detecting an association between allergen reactivity and Ascaris infection. Those who seek medical help may also have a greater sense of hygiene, and hence any estimate of prevalence of parasitosis in the group may underestimate that of the general population. Alternatively the more hygiene-conscious individual may stay well away from the government hospital environment, preferring to attend private clinics, and thereby distort the findings in the opposite direction! This may be important, as it has been suggested that the level of parasitic burden may determine its effect on the allergic phenotype [ 29]. In areas where parasite levels are only moderate, parasite infestation has been found to exacerbate the allergic response [ 30], whereas in populations where parasite burden is heavy, parasitic infestation appears to downregulate the same response [ 34]. Another constitutional factor, which may be important in determining the immune response, is the nutritional status of the host. It seems very likely that malnutrition causes immunosuppression, and hence may affect both the antiparasite and the allergic response. In Venezuelan Ascaris-infected children the specific anti-Ascaris antibody response was significantly lower in the malnourished group, whereas the total IgE and IL-4 levels were significantly higher. This pattern of antibody response fits with malnourishment being associated with an increased susceptibility to parasites in this tropical environment. The nutritional status of the subjects in the current study [ 19] was not assessed. Thus this new study adds further evidence that exposure and/or immunity to parasitic infestation appears to be associated with a reduced risk of asthma, and also provides more weight to the growing evidence that sensitization to dust mite is an important risk factor for asthma in urbanized African communities. However, the study does not help us to understand why atopy appears to be less strongly related to asthma in more rural areas, and it also does not define the nature of the cause and effect relationship in the parasite–allergy association. To resolve these issues we need studies that measure exposure and sensitivity to environmental allergens, intestinal parasite burden and the immunological response to both the allergens and parasites. Ideally, such studies should also be able to investigate the importance of the timing of these various exposures in a longitudinal cohort, and will need to collect information on confounders such as nutritional status and other socioeconomic factors. In conclusion, the role of IgE in allergic disease, and the influence of parasites on this relationship, is clearly very important, and this fascinating subject is in great need of further investigation.

British Journal of UrologyVolume 82, Issue 4 p. 597-598 Splenic metastasis from adenocarcinoma of the prostate Naseem, Naseem Urology, St Bartholomew’s Hospital, London, UKSearch for more papers by this author Jan, Jan Departments of Nuclear Medicine,Search for more papers by this author Britton, Britton Departments of Nuclear Medicine,Search for more papers by this author Nargund, Nargund Urology, St Bartholomew’s Hospital, London, UKSearch for more papers by this author Naseem, Naseem Urology, St Bartholomew’s Hospital, London, UKSearch for more papers by this author Jan, Jan Departments of Nuclear Medicine,Search for more papers by this author Britton, Britton Departments of Nuclear Medicine,Search for more papers by this author Nargund, Nargund Urology, St Bartholomew’s Hospital, London, UKSearch for more papers by this author First published: 04 January 2002 https://doi.org/10.1046/j.1464-410X.1998.00786.xCitations: 11 Mr Naseem Department of Urology, King George V Building, St Bartholomew’s Hospital, West Smithfield, London EC1 A7BE, UK. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume82, Issue4October 1998Pages 597-598 RelatedInformation

In studies of asthma prevalence bronchial responsiveness has usually been measured as the provocative dose of bronchoconstrictor causing a 20% fall in FEV1 (PD20FEV1). This is relatively insensitive and only 10-20% of subjects in a general population sample will show such a response. Attempts to increase sensitivity, such as the use of the provocative dose causing a 10% fall in FEV1 (PD10FEV1), have not demonstrated any overall advantage, due to poorer repeatability. It has been suggested that measurement of bronchial reactivity using flow at low lung volumes measured from a partial flow volume curve is a more sensitive index of bronchoconstriction than PD20FEV1. If equally repeatable, it would have advantages in epidemiological practice. In 20 subjects with asthma, we compared the sensitivity and repeatability of PD10FEV1, PD20FEV1, and the provocative dose causing a 40% fall in flow at 30% of vital capacity (PD40V30P) following methacholine challenge. PD40V30P was more sensitive than both PD20FEV1 and PD10FEV1 by 1.48 and 0.35 doubling doses (DD) of methacholine, respectively. PD20FEV1 and PD40V30P showed equal repeatability, the 95% range for a single estimate of both being 2.02 DD. PD10FEV1 was less repeatable, with a 95% range of 2.35 DD. Values for the intraclass correlation co-efficient, which measures the ability of a test to discriminate between subjects, were 0.63, 0.79 and 0.69 for PD10FEV1, PD20FEV1, and PD40V30P, respectively. The increased sensitivity and comparable repeatability of measurement of bronchial reactivity for PD40V30P suggest that this method may be useful for studies of asthma prevalence.

This paper examines the relationship between smoking levels and blood pressure patterns of normotensive pregnant women in a prospective cohort of 2193 primiparous and 3176 multiparous, normotensive, Caucasian women selected from the Child Health and Development Studies in Oakland, California, 1959-67. Regression lines were fitted to each woman's blood pressure; mean intercept and slope estimates of the individual regressions were used to create summary profile lines for each smoking dose. Multivariable regression analysis controlled for maternal age, number of visits to the doctor after 20 weeks' gestation, body mass index and maternal education level. Overall, smokers had lower average diastolic blood pressure (smokers vs. nonsmokers adjusted mean: primiparas, 66.1 vs. 67.2 mmHg; and multiparas, 64.0 vs. 64.7 mmHg) but higher systolic blood pressure (smokers vs. nonsmokers adjusted mean: primiparas, 117.0 vs. 116.0; and multiparas, 112.5 vs. 110.0) than nonsmokers among primiparous and multiparous pregnant women after adjusting for potential confounders. However, these differences are small and there was no clear dose-response relationship between smoking level and blood pressure.

This memorandum constitutes our September 2015 level 4 milestone for the project entitled “Johnson Noise Thermometry for Drift-free Temperature Measurements” and satisfies the Milestone/Activity (Conclude HFIR field demonstration of JNT prototype). The progress summary describes the work performed to complete the subject milestone.

石榴水果皮富于 bioactive 植物天赋产品，例如 hydrolyzable 丹宁和 anthocyanins。尽管有他们在人的营养和水果质量的记录角色，涉及自然产品生合成的基因没从石榴被克隆，很小的顺序信息在在公共领域的石榴上是可得到的。石榴水果皮 cDNA 定序的猎枪 transcriptome 在 Illumina 染色体分析器站台上用 RNA-Seq 被执行。超过 1 亿个未加工的序列读被获得并且集合进 9,839 个 transcriptome 集会(TA )(> 200 bp ) 。为 hydrolyzable 丹宁， anthocyanin， flavonoid， terpenoid 和丰满的酸生合成或规定的候选人基因被识别。三类脂化合物转移蛋白质被获得那可以贡献石榴水果摘录的以前报导的 IgE 反应。另外， 115 个 SSR 标记从石榴水果皮 transcriptome 被识别，教材为 77 个 SSR 标记被设计。石榴水果皮 transcriptome 集合在石榴为自然产品 biosynthetic 基因和 SSR 标记发现提供一个珍贵平台。这个工作也证明定序的下一代的 transcriptome 是为调查自然产品生合成的一条节俭、有效的途径，识别控制重要农学的特点，并且发现在非模型特长庄稼种类的分子的标记的基因。

Illustrated book of the film. Includes 'Facts about the Film' and biographies of main cast members

Phase II was originally planned as a series of field tests to confirm the results of the sampling methods performance tests conducted during Phase I. However, the API Chapter 14.1 Gas Sampling Research Working Group chose to have the tests conducted at a newly developed wet gas test facility located at the Colorado Engineering Experiment Station (CEESI), in Nunn, Colorado. Three general tests were conducted. Test Plan I was intended to investigate the effects of sample point location on on-line gas chromatograph (GC) analyses and on spot sampling methods. Test Plan II was intended to investigate the effects of sample point location on on-line GC analyses and to compare several spot sampling methods when sampling from the same point. Test Plan III was intended to investigate the effects of coupling configurations and cylinder temperature on two specific methods: Helium Pop, and purging - Fill/Empty.