bluuebunny/crossref_metadata_2025 huggingface dataset:
Experience of surgery for rectal cancer with total mesorectal excision in a general surgical practice
Authors: Dowdall J F , Maguire D , McAnena O J
Published: March 2003

Background

Results from specialist centres have shown that total mesorectal excision (TME) produces excellent control of local disease in patients with carcinoma of the rectum.

Methods

The results of TME were reviewed in a surgical practice in which patients with rectal cancer comprised 1 per cent of the total caseload and mean case numbers were less than 15 each year.

Results

Eighty-two consecutive patients underwent rectal excision with TME over a 72-month period (68 anterior resection, eight abdominoperineal excision and six Hartmann's procedure). Sixty-nine operations were deemed ‘curative’ at the time of surgery. Anastomotic leak occurred in two (3 per cent) of 68 patients, both of whom recovered without additional surgery. There were two local recurrences (3 per cent) among 69 patients who underwent ‘curative’ surgery. At a median follow-up of 190 weeks, the survival rate for Dukes' stage A, B, C and ‘D’ was 100, 83, 68 and 18 per cent respectively.

Conclusion

Outcome as measured by perioperative morbidity and local disease control achieved in a surgical practice with a broad case mix and relatively low annual case volume was comparable to that from larger centres. Appropriate surgical training and attention to technical detail may be as important as case volume in determining outcome after surgery for rectal cancer.
Antisense oligonucleotides targeted against protein kinase c α inhibit proliferation of cultured avian myoblasts
Authors: Capiati D. A. , Vazquez G. , Tellez Iñón M. T. , Boland R. L.
Published: March 2003

Protein kinase C (PKC) has been implicated in the control of proliferation and differentiation of many cell types. There is evidence indicating that it plays a role in signal transduction mechanisms related to myogenesis, but little is known about the individual functions of PKC isoforms in muscle cell development. Data obtained in previous studies using cultured chick embryo skeletal muscle cells suggested that PKC α is linked to the regulation of myoblast proliferation. However, this causal relationship could not be definitively established as no experiments based on selective inhibition of this isoform were carried out. In the present work, specific inhibition of the expression of PKC α in cultured myoblasts by using antisense oligonucleotide technology resulted in a significant decrease of culture cell density and DNA synthesis, clearly showing that this isoenzyme is involved in signalling pathways which promote muscle cell proliferation.
p53 functional assays: detecting p53 mutations in both the germline and in sporadic tumours
Authors: Camplejohn R.S. , Rutherford J.
Published: March 2003

The tumour suppressor gene p53 is the gene most often reported to be mutated in clinical cancers with something like half of all tumours harbouring mutations. Further, many studies have suggested that p53 mutations have prognostic importance and sometimes are a significant factor in determining the response of tumours to therapy. The value of knowing the p53 status of individual tumours will increase if currently researched strategies aimed at developing p53‐based treatment protocols come to fruition. There are quite a number of techniques used to detect p53 defects in both tumours and in the germline of cancer‐prone families, although some of these methods are indirect and each has certain drawbacks. In this brief review we will discuss the value of two assays of p53 function as a means of detecting and partly characterizing p53 mutations. The two assays are the apoptotic assay, which measures the response of peripheral blood lymphocytes to radiation‐induced DNA damage and the FASAY, a yeast based assay which assesses the ability of a given p53 protein to transactivate p53 target genes. Both of these assays are rapid, yielding results within 5 days. Further, they not only offer the possibility of detecting p53 mutations but also of characterizing a given mutation in terms of two of p53’s most important functions, namely the induction of apoptosis and the transactivation of target genes.
Extracellular matrix alters the relationship between tritiated thymidine incorporation and proliferation of MC3T3‐E1 cells during osteogenesisin vitro
Authors: Peterson W. J. , Tachiki K. H. , Yamaguchi D. T.
Published: March 2003

Bone cellsin vivoexist in direct contact with extracellular matrix, which regulates their basic biological processes including metabolism, development, growth and differentiation. Thus, thein vitroactivity of cells cultured on tissue culture treated plastic could be different from the activity of cells cultured on their natural substrate. We selected MC3T3‐E1 pre‐osteoblastic cells to study the effect of extracellular matrix on cell proliferation because these cells undergo a progressive developmental sequence of proliferation and differentiation. MC3T3‐E1 cells were cultured on plastic or plastic coated with ECM, fibronectin, collagen type I, BSA or polyl‐lysine and their ability to proliferate was assessed by incorporation of [3H]dT or by enumeration of cells. Our results show that (1) ECM inhibits incorporation of [3H]dT by MC3T3‐E1 cells; (2) collagen type I, but not BSA, polyl‐lysine or fibronectin also inhibits incorporation of [3H]dT; (3) the level of ECM inhibition of [3H]dT incorporation is directly related to the number of cells cultured, but unrelated to the cell cycle distribution or endogenous thymidine content; (4) the kinetic profile of [3H]dT uptake suggest that ECM inhibits transport of [3H]dT from the extracellular medium, and (5) cell counts are similar in cultures whether cells are grown on plastic or ECM. These results suggest that decreased incorporation of [3H]dT by cells cultured on ECM is not reflective of bone cell proliferation.
X‐irradiation effects on thymidine kinase (TK): II. The significance of deoxythymidine triphosphate for inhibition of TK1 activity
Authors: He Q. , Skog S. , Welander I. , Tribukait B.
Published: March 2003

Abstract. The purpose of this study was to investigate the mechanism behind the high sensitivity of thymidine kinase 1 (TK1) to X‐irradiation. The deoxythymidine triphosphate (dTTP) pool was studied in mouse ascites tumour cells 1–24 h after X‐irradiation with 5 Gy. Irradiation changed the Michaelis‐Menten kinetics of TK1 from linear to biphasic, showing a negative co‐operativity. These changes were closely related to changes in the dTTP pool. Addition of dTTP to the cell extract of non‐irradiated cells, or thymidine (dTdR) to the culture medium, resulted in changes very similar to the kinetics found in the irradiated cells. Addition of 5¢‐amino‐5¢‐deoxythymidine (5¢‐AdTdR), a thymidine analogue that eliminated the inhibitory effect of dTTP on TK1 activity, completely abolished the irradiation‐induced inhibition of TK1 activity. We suggest that the reduced TK1 activity is mainly due to an elevated intracellular concentration of dTTP.
Exogenous cysteine and cystine promote cell proliferation in CaCo‐2 cells
Authors: Noda T. , Iwakiri R. , Fujimoto K. , Rhoads C. A. , Aw T. Y.
Published: March 2003

Abstract. Previous studies have shown that intracellular glutathione, a ubiquitous intracellular thiol, is related to cell proliferation and that cysteine or its disulphide form, cystine, also induces cell proliferation. Cysteine is a thiol containing amino acid and a rate‐limiting precursor of glutathione. Therefore, it is still unresolved as to whether the proliferative effect of cysteine or cystine is entirely mediated by a change in the intracellular glutathione status. The objective of this study was to delineate the relationship among cysteine/cystine (thereafter referred to as cyst(e)ine), intracellular glutathione and cell proliferation in the human colon cancer CaCo‐2 cell line. CaCo‐2 cells were cultured in cyst(e)ine‐free Dulbecco’s Modified Eagle Medium without serum, and treated with 200 µm cysteine and/or 200–400 µm cystine for 24 h. In the presence of DL‐buthionine‐[S, R]‐sulfoximine (BSO), a glutathione synthesis inhibitor, exogenously administered cyst(e)ine did not change the intracellular glutathione content, but increased the intracellular cysteine as well as cystine level. Addition of exogenous cyst(e)ine following 5 mm BSO treatment significantly increased cell proliferation as measured by 3H‐thymidine incorporation and protein content. Cell cycle analyses revealed that cyst(e)ine promoted cell progression from the G1 phase to the S phase. Correspondingly, cyst(e)ine treatment induced expression of cyclin D1 and phosphorylation of retinoblastoma protein (Rb). In conclusion, these data indicate that both cysteine and cystine have proliferative effects in CaCo‐2 cells independent of an increase in intracellular glutathione. Induction of cyclin D1, phosphorylation of Rb, and subsequent facilitation of G1‐to‐S phase transition were involved in the proliferative effect of exogenous cyst(e)ine.
Cell kinetic studies in the murine ventral tongue epithelium: thymidine metabolism studies and circadian rhythm determination
Authors: Potten C. S. , Booth D. , Cragg N. J. , Tudor G. L. , O'Shea J. A. , Appleton D. , Barthel D. , Gerike T. G. , Meineke F. A. , Loeffler M. , Booth C.
Published: March 2003

Abstract.  The oral mucosa is a rapidly replacing body tissue that has received relatively little attention in terms of defining its cell kinetics and cellular organization. The tissue is sensitive to the effects of cytotoxic agents, the consequence of which can be stem cell death with the subsequent development of ulcers and the symptoms of oral mucositis. There is considerable interest in designing strategies to protect oral stem cells and, hence, reduce the mucositis side‐effects in cancer therapy patients. Here we present details of a new histometric approach designed to investigate the changing patterns in cellularity in the ventral tongue mucosa. This initial paper in a series of four papers presents observations on the changing patterns in the labelling index following tritiated thymidine administration, which suggest a delayed uptake of tritiated thymidine from a long‐term intracellular thymidine pool, a phenomenon that will complicate cell kinetic interpretations in a variety of experimental situations. We also provide data on the changing pattern of mitotic activity through a 24‐h period (circadian rhythms). Using vincristine‐induced stathmokinesis, the data indicate that 54% of the basal cells divide each day and that there is a high degree of synchrony in mitotic activity with a mitotic peak occurring around 13.00 h. The mitotic circadian peak occurs 9‐12 h after the circadian peak in DNA synthesis. The data presented here and in the subsequent papers could be interpreted to indicate that basal cells of BDF1 mice have an average turnover time of about 26‐44 h with some cells cycling once a day and others with a 2‐ or 3‐day cell cycle time.
Cell kinetic studies in murine ventral tongue epithelium: cell cycle progression studies using double labelling techniques
Authors: Potten C. S. , Booth D. , Cragg N. J. , O'Shea J. A. , Tudor G. L. , Booth C.
Published: March 2003

Abstract. The dorsal and ventral epithelia on the murine tongue exhibit very pronounced circadian rhythms in terms of the cell cycle. These rhythms are such that three injections of tritiated thymidine 3 h apart spanning the circadian peak in S phase cells labelled between 40 and 50% of the basal cells. Injection of bromodeoxyuridine generally gave slightly lower labelling indices. Approximately the same proportion (54% of the basal cells) could be accumulated in metaphase over a 24‐h period using vincristine as a stathmokinetic agent. The experiments reported here using mouse ventral tongue epithelium use double‐labelling approaches to address the question: what proportion of the approximately 50% of the basal cells that are proliferating have a 24‐h cell cycle and can therefore be labelled by a similar labelling protocol the following day? The results suggest a heterogeneity amongst the proliferating basal cells, similar to the heterogeneity proposed for the dorsal tongue epithelium. Although not all the basal component has been accounted for, the data presented here suggest that about 20% of the basal cells may have a cell cycle time of 24 h, about 30% appear to have a longer cell cycle time (48 or 72 h), while about 20% of the basal cells appear to be postmitotic maturing G1 cells, awaiting the appropriate signals for migration into the suprabasal layer.
The effect of keratinocyte growth factor on healing of manifest radiation ulcers in mouse tongue epithelium
Authors: Dörr W. , Spekl K. , Farrell C. L.
Published: March 2003

Abstract. The purpose of this study was to examine the effect of recombinant human keratinocyte growth factor (rHuKGF) on clinically manifest acute oral mucositis. The animal model utilized in this investigation was ventral tongue epithelium of C3H/Neu mice. In a first experiment, graded single doses were applied in order to define dose effect and time course of acute mucosal ulceration, as a clinically relevant endpoint. Irradiation was given to a 3 × 3 mm2 test field in the centre of the ventral tongue with 25 kV X‐rays. A single dose of 18 Gy, i.e. a dose after which ulceration is expected in more than 99% of the animals, was applied in subsequent experiments. In the study group of 20 animals, rHuKGF was applied at a daily dose of 5 mg/kg subcutaneously from the time of first diagnosis of ulcer for a maximum of 5 days. In the control group, phosphate‐buffered saline was used as a placebo. The time course of ulceration, i.e. individual ulcer duration, was analysed in both the control group without rHuKGF and the study group. Irradiation with graded single doses yielded an ED50 of 11.5 ± 0.7 Gy (logit analysis). In responding animals, the latent time to first diagnosis of ulceration and the individual ulcer duration were independent of dose. Mean latency (± standard deviation) was 10.5 ± 0.5 days, mean ulcer duration 3.9 ± 0.6 days for doses 11, 13 and 16 Gy. After a dose of 18 Gy, 39 animals developed ulceration after a mean latency of 9.3 ± 0.3 days (control and KGF‐treated). The average ulcer duration was 4.2 ± 0.9 days in the placebo group and 4.8 ± 0.8 days in the KGF group (P = 0.02). We conclude that when rHuKGF treatment is delayed until radiation‐induced ulcers are manifest, the therapeutic activity previously reported with other treatment schedules was not observed and there was a slight prolongation of duration of ulceration. These data suggest that during tumour radiotherapy, effective rHuKGF therapy schedules should include administration before the onset of ulcerative mucositis.
Parenting efficacy, aggressive parenting and cultural connections
Authors: Ortega D.M.
Published: March 2003

This paper describes an exploratory study examining parenting efficacy, behaviours related to child–parent conflict and cultural connection. Fifty‐four low‐income mothers from diverse cultural backgrounds responded to a questionnaire that included the Parental Locus of Control Scale, the Conflict Tactic Scale, and a composite scale measuring the degree that mothers were connected to their self‐identified culture. Non‐parametric statistical measures were used to analyse study data. Results indicate differences between ‘high’ and ‘low’ culturally connected mothers on parenting measures. Mothers with ‘high’ cultural connection were less aggressive parents and felt more responsible for their child’s behaviour.
Residential institutions requesting supervision: a theoretical analysis of an empirically studied problem
Authors: Fyhr G.
Published: March 2003

This study was based on vague but persistent problems of uncertain origin permeating treatment and care in Swedish residential institutions treating emotionally disturbed and socially disadvantaged children. The purpose was to generate a reliable, empirically grounded theory, sufficient to describe and explain these problems, which were first observed in supervisory sessions. The main methods used were grounded theory (Glaser & Strauss 1967; Strauss & Corbin 1990, 1998) and abduction (Peirce 1914/1990; Fann 1970; Josephson & Josephson 1996). During a three‐year period, 17 respondents from three strategically chosen institutions were individually interviewed twice. The results suggest that artificial family institutions, enjoying family privileges, may develop out of family ideas. Under certain conditions, such institutions may be transformed into non‐professional institutions that fail to carry out their official task, but that instead effect unconscious psychological tasks – tasks that are both hidden behind and obstruct the institution’s official mission. The possibility of avoiding this development is dependent partly on the quality of the emotional content, called the need for reparation, within the institution, and partly on the methods used to control this need. This notion was tested in practice in a separate part of the study in which the method action‐cum‐research (Trankell 1973) was used. One of the studied institutions was then observed for two years during a process of planned change in organization, treatment routines and attitudes. After two years, the final resistance to the official task had disappeared, and the former non‐professional institution now worked in a task‐orientated manner. This result has broad implications for planning and support of care institutions, as the same phenomena might arguably occur in any care organization.
Blame and family conflict: symptomatic children as scapegoats
Authors: Yahav Rivka , Sharlin Shlomo A.
Published: March 2003

The study’s aim was to examine the relation between children’s symptom type, specifically externalized vs. internalized symptoms, and children’s perception of being blamed by family members for various family conflicts. The research hypothesis was based on theories of family therapy, in particular on the concept of scapegoating and projective identification processes. The subjects were chosen from treatment centres for children and adolescents, using the Achenbach Self‐Report Questionnaire. Subjects included males and females, aged 10–17, who had either internalized or externalized symptoms and no history of organic or psychotic disorders. The control group consisted of non‐symptomatic children. The research groups also included each child’s sibling closest in chronological age, who served as an additional control group. A total of 161 children participated in the study. It was found that externalizing children reported greater subjection to parental blame than did the other children.
Developmental disorders of glucose metabolism in infants
Authors: Hume R. , McGeechan A. , Burchell A.
Published: March 2003

Background Developmental failures to adequately control postnatal blood glucose levels are common in the transition from fetal to infant life and can persist for many months. The standard method of functionally measuring hepatic glucose production and/or disordered glucose production is the response to a glucagon tolerance test.

Method We adapted the standard glucagon tolerance test used for children and adults for use in preterm infants. 79 consecutive preterm infants gestational age range 25–36 weeks (mean 32.2 weeks), mean birth weight 1.66 kg admitted to the Neonatal Intensive Care Unit, Ninewells Hospital, Dundee and who survived to discharge home were recruited into the study. At the time of discharge home the characteristics of the group were as follows: adjusted mean gestational age 36.7 weeks, mean discharge weight 2.23 kg.

Results In this study of preterm infants the maximal increase in plasma glucose following administration of a glucagon tolerance test is 1.39 ± 07 mmol/L, n = 78 (range 0–3.98 mmol/L).

Conclusions An increase in plasma glucose of less than 4 mmol/L is considered abnormal in adults following administration of a fasting glucagon tolerance test. The responses of preterm infants and adults to glucagon are clearly different. The attenuated response to glucagon in the preterm infants is consistent with the low levels of hepatic glucose‐6‐phosphatase activity in premature infants as glucose‐6‐phosphatase is the terminal step of the two main pathways of liver glucose production.
Secondary school accident reporting in one education authority
Authors: Williams W.R. , Latif A.H.A. , Sibert J
Published: March 2003

Background
Secondary schools appear to have very different accident rates when they are compared on the basis of accident report returns. The variation may be as a result of real differences in accident rates or different reporting procedures. This study investigates accident reporting from secondary schools and, in particular, the role of the school nurse.

Methods
Accident form returns covering a 2‐year period were collected for statistical analysis from 13 comprehensive schools in one local education authority in Wales. School sites were visited in the following school year to obtain information about accident records held on site and accident reporting procedures.

Results
The main factors determining the number of school accident reports submitted to the education authority relate to differences in recording and reporting procedures, such as the employment of a nurse and the policy of the head teacher/safety officer on submitting accident returns. Accident and emergency department referrals from similar schools may show significant differences in specific injuries and their causes.

Conclusions
The level of school accident activity cannot be gauged from reports submitted to the education authority. Lack of incentives for collecting good accident data, in conjunction with the degree of complacency in the current system, suggest that future accident rates and reporting activity are unlikely to change.
Motor performance and behaviour in preterm and full‐term 3‐year‐old children
Authors: Hemgren E. , Persson K.
Published: March 2003

Aim To compare the motor performance and behaviour at 3 years of age of very preterm,
moderately preterm and full‐term children (n = 221), who needed neonatal intensive care (NIC), and of 72 neonatally healthy full‐term children (reference group).

Method A model for combined assessment of motor performance and behaviour (CAMPB) was used. The children’s performance was assessed on the basis of observations and documentation of categories of co‐ordination, attention and social behaviour included in CAMPB.

Results Significantly more very preterm children showed deviations in co‐ordination than children in the other groups, and this difference was most evident in comparison with the reference group. No differences were found between the groups regarding attention and social behaviour during the assessment.

Conclusion Very preterm children differ from moderately preterm and full‐term children in their motor performance at 3 years of age. By means of CAMPB, individual children with pronounced inco‐ordination were identified in all groups, and some of them also showed pronounced lack of attention.
Health of children considered for adoption
Authors: Colver A. F. , Gale C. , Appleby L.
Published: March 2003

Children in the ‘care’ system are known to have poor health. Although health services can respond to and deal with health problems, it is parents, foster parents and social workers who recognize problems, seek advice and keep follow‐up appointments. Many health needs remain unmet in such children. This short paper from a deprived area in north‐east England shows that once a decision is made to proceed to adoption, the stable and consistent care that can then be provided meets the increased health needs that such children have.
Detecting emotional and behavioural problems in paediatric clinics
Authors: Glazebrook C. , Hollis C. , Heussler H. , Goodman R. , Coates L.
Published: March 2003

Background  Children with chronic illness have increased rates of mental health problems and psychological difficulties often present as physical conditions. This prevalence survey aims to determine whether children attending general paediatric out‐patient clinics are at increased risk of suffering from emotional and behavioural disturbance and whether there is an unmet need for psychiatric liaison to paediatric clinics.

Methods  Participants were 307 children aged 5–15 years attending a representative sample of paediatric out‐patient clinics in one UK hospital. A national community sample of 10 438 children aged 5–15 years was used as a comparison group. Parental ratings of child behaviour were obtained using the Strengths and Difficulties Questionnaire (SDQ). Doctors rated the extent of any emotional difficulties using a modification of the SDQ ‘impact supplement’.

Results  Children attending paediatric out‐patient clinics were more than twice as likely (OR = 2.3, 95% CI 1.7–3.1) to score in the abnormal range of the SDQ. Of the 60 (20%) children with a probable psychiatric disorder only 15 had received specialist help from Child Mental Health Services. There were no gender differences in the profile of difficulties with emotional symptoms being particularly evident in both boys (OR = 2.85, 95% CI 1.97–4.11) and girls (OR = 3.04, 95% CI 1.92–4.70). The risk of psychiatric disorder was highest among those children with brain disorders attending neurological clinics (OR = 5.8, 95% CI 2.5–11.3). Clinicians only identified emotional or behaviour problems in a quarter of those children with parent‐rated disorder.

Conclusion  There is an increased prevalence of emotional and behavioural disturbance in children attending paediatric out‐patient clinics. The SDQ could be added to routine paediatric assessments to aid appropriate referral of children with a possible psychiatric disorder to child mental health services.
Linkage and allelic association of atopy and markers flanking the IL4‐receptor gene
Authors: Deichmann K. A. , Heinzmann A. , Forster J. , Dischinger S. , Mehl C. , Brueggenolte E. , Hildebrandt F. , Moseler M. , Kuehr J.
Published: March 2003

Background

Atopy, a clinical syndrome characterized by heightened IgE responsiveness, is largely determined by genetic factors. The disease may well be heterogeneous but the mode of inheritance is unknown. Several genes have been named which affected IgE responsiveness. However, results are conflicting reflecting heterogeneity and a complicated inheritance pattern of the atopic syndrome. In 1994 linkage of the 5q32 gene region and elevated total IgE levels were reported, leaving the IL4 gene as a prominent candidate.

Objectives

We were interested in a possible involvement of the IL4‐receptor gene in the development of atopy.

Methods

We employed sib‐pair linkage analysis using highly polymorphic microsatellite markers within and flanking the IL4 receptor gene in atopic families, characterized for specific sensitization to inhalant allergens and elevated total serum IgE. Allele sizes were determined for all microsatellite probes to allow transmission disequilibrium analysis.

Results

We found significant sharing of maternal but not paternal alleles in affected sibs from two independent populations, both of which presented enhanced IgE responsiveness. Linkage and maternal inheritance could be confirmed by transmission disequilibrium analysis.

Conclusions

We conclude from our findings that maternal inheritance of a gene in the chromosome 16p12 region increases the risk for enhanced IgE responsiveness. The most prominent candidate in this region is represented by the IL4 receptor gene.
Comparison of nasal mucosal responsiveness to neuronal stimulation in non‐allergic and allergic rhinitis: effects of capsaicin nasal challenge
Authors: Sanico  , Philip  , Proud  , Naclerio  , Togias
Published: March 2003

Background

Neuronal involvement has been implicated in the pathophysiology of non‐allergic and allergic rhinitis, contributing to the typical exacerbation of these conditions upon exposure to non‐specific environmental irritants.

Objectives

To determine if non‐allergic and allergic rhinitis are characterized by increased responsiveness of the nasal mucosa to sensorineural stimulation.

Methods

Nasal challenges with capsaicin and its vehicle were performed in three groups of subjects — non‐allergic rhinitics, perennial allergic rhinitics, and healthy controls — and resultant symptom scores, glandular secretion reflected by lactoferrin levels, and plasma extravasation reflected by albumin levels in nasal lavage fluid were compared.

Results

Capsaicin‐sensitive nerve stimulation produced increases in symptom scores and lactoferrin levels which were similar among the three groups of subjects. On the other hand, only the group of subjects with allergic rhinitis demonstrated a significant capsaicin‐induced increase in albumin levels and a trend in total protein levels.

Conclusions

We conclude that nonallergic rhinitis is not characterized by increased responsiveness of capsaicin‐sensitive nerve fibres; while allergic rhinitis is marked by hyperresponsiveness manifested as increased albumin leakage in nasal fluids. This may reflect the activity of an axonal reflex to sensorineural stimulation.
Occupational asthma in fruit salad processing
Authors: Sen  , Wiley  , Williams
Published: March 2003

Background

Three subjects employed in the preparation of fruit for fruit salads reported work‐related respiratory symptoms. Their work entailed removing the peel from citrus fruits, primarily oranges, following soaking of the fruits in a bath of enzymes including fungal derived pectinase and glucanase.

Objectives

To investigate the respiratory symptoms reported by these workers and determine their causes.

Methods

The three workers were investigated by a respiratory physician, including spirometry and serial peak flow measurements. Blood was taken for the measurement of IgE and IgG antibody responses against the enzyme solution.

Results

Predominant symptoms in these workers were shortness of breath, chest tightness and wheezing which were all alleviated at weekends and holidays only to occur when returning to work. Serial peak flow measurements showed a clear work‐related pattern. All three had strong IgE responses to the enzyme solution used at the workplace and showed distinct patterns of binding in immunoblots. All three improved immensely following withdrawal from the workplace environment.

Conclusion

Enzymes appear to be widely used in the preparation of fruit and although they are used in liquid form, exposure can occur to induce immunological sensitization and asthma.
Perinatal risk factors for atopic disease in conscripts
Authors: BRÅBÄck  , Hedberg
Published: March 2003

Background

There is evidence to suggest that atopic disease in adulthood could be manifestations of events in early life.

Objectives

To investigate the relationship between perinatal risk factors and the prevalence of allergic rhinitis and asthma in conscripts.

Methods

A retrospective cohort study, where information from the Military Service Enrolment Register was linked to the national Medical Birth Register. The study included 149 398 male conscripts who were born in Sweden in 1973, 1974 and 1975. Outcome measures were current asthma and allergic rhinitis recognized at the compulsory military conscript examinations.

Results

Unifactorial analyses demonstrated that number of older siblings, young maternal age, multiple gestation, prematurity, low birth weight, growth retardation and perinatal asphyxia were all significantly related to a decreased risk of allergic rhinitis among male conscripts. The prevalence rates of allergic rhinitis among conscripts with and without older siblings were 14.1% and 16.2%, respectively (odds ratio 0.85; 95% confidence interval 0.82–0.87). The prevalence rates of allergic rhinitis among those with term birth (>36 weeks), moderately preterm birth (33–36 weeks) and very preterm birth (<33 weeks) were 15.2%, 13.1% and 11.6%, respectively. Older siblings, multiple gestation and young maternal age were highly significant independent determinants of allergic rhinitis. By contrast, the effects of prematurity, low birthweight and asphyxia were weaker and highly correlated. The only independent determinants of asthma were maternal age, birthweight and multiple gestation. Furthermore, maternal age and birthweight had opposite effects on asthma and allergic rhinitis.

Conclusions

In contrast to asthma, allergic rhinitis in young adult men was strongly associated with perinatal events. This may reflect the close relationship between allergic rhinitis and atopic sensitization, whereas asthma has a more multifactorial aetiology.
Effects of long‐term oral treatment with leflunomide on allergic sensitization, lymphocyte activation, and airway inflammation in a rat model of asthma
Authors: Uhlig  , Cooper  , Eber  , Mcmenamin  , Wildhaber  , Sly
Published: March 2003

Background

Short‐term treatment with leflunomide is effective in suppressing antigen‐specific antibody production and allergen‐induced bronchoconstriction after sensitization. This agent may thus have a role in future primary prevention strategies in allergic disease.

Objective

The current study aimed to determine whether long‐term oral treatment with leflunomide prevents allergic sensitization permanently.

Methods

After sensitization with ovalbumin, six groups of rats (n = 31) were treated daily with leflunomide or diluent for up to 30 days. Ovalbumin‐specific IgE and IgG were determined weekly for at least 2 weeks after cessation of treatment. T lymphocytes from another 21 animals were stimulated ex vivo with ovalbumin or concanavalin A.

Results

Ovalbumin‐specific IgE and IgG were lower during treatment with leflunomide compared with controls (P < 0.002) but increased after the cessation of treatment. Antigen‐specific T‐cell proliferation was decreased in cells obtained from leflunomide treated animals (P < 0.05), but not when stimulated with concanavalin A. Eosinophil (P < 0.0001) and neutrophil (P < 0.02) numbers in bronchoalveolar lavage 24 h after allergen challenge were lower in the leflunomide treated animals.

Conclusions

Leflunomide prevents antigen‐specific immunoglobulin production after sensitization during treatment, inhibits allergen‐induced airway inflammation and diminishes antigen‐specific T lymphocyte proliferation.
Study of a case of hypersensitivity to lettuce (Lactuca sativa)
Authors: Vila  , SÁnchez  , Sanz  , DIÉguez  , MartÍnez  , Palacios  , MartÍnez
Published: March 2003

Background

Allergic reactions to lettuce (Lactuca sativa) are not too frequent and few cases of systemic adverse reactions after its ingestion have been described.

Objective

We report a case of clinical sensitization to lettuce on a patient who presented mucocutaneous manifestations after its ingestion, with positive skin tests, histamine release test and serum specific‐IgE to lettuce. The allergens responsible for this sensitization were also characterized by means of SDS‐PAGE immunoblotting.

Materials and methods

We performed skin tests, histamine release test, serum specific IgE determination and CAP inhibition with lettuce and mugwort (Artemisia vulgaris) extracts. An aqueous and enriched lettuce (from loose leaf type) extract was subjected to SDS‐PAGE immunoblotting for determination of its IgE‐binding components.

Results

and Conclusions CAP inhibition showed antigenic community between lettuce and mugwort. Four protein bands from the lettuce extracts with molecular weights of 50, 43, 39 and 16 kDa exhibited IgE‐binding properties.
The long‐term influence of therapeutic interventions in asthma with emphasis on inhaled steroids and early disease
Authors: Haahtela
Published: March 2003

The data available to show the long‐term benefits of any pharmacological interventions in asthma is scanty. Usually the beneficial effects disappear gradually when the treatment is withdrawn. The evidence showing that treatment with drugs could change the natural course of asthma is largely lacking. Only a few controlled studies have lasted more than 1 year, while asthma can be a disease for life. Nevertheless, the short‐term benefits of treatment with inhaled steroids justify their introduction as soon as the diagnosis of asthma is established. Regular use of inhaled steroids especially during the early stages of asthma often makes it a less troublesome disease. Regular use of long‐acting β2‐agonists is useful in preventing exacerbations in persistent asthma, but their influence on the long‐term outcome is quite unknown. Exploration of the possible disease outcome modifying effect of new innovations such as leukotriene antagonists should be put in the clinical study programmes. In future, the combination of immunological and pharmacological treatments may offer the key for more permanent results in asthma therapy.
Selective phosphodiesterase inhibitors for the treatment of bronchial asthma and chronic obstructive pulmonary disease
Authors: Schmidt D. , Dent G. , Rabe K. F.
Published: March 2003

Theophylline is commonly used in the treatment of obstructive airway diseases. The identification and functional characterization of different phosphodiesterase (PDE) isoenzymes has led to the development of various isoenzyme‐selective inhibitors as potential anti‐asthma drugs. Considering the distribution of isoenzymes in target tissues, with high activity of PDE3 and PDE4 in airway smooth muscle and inflammatory cells, selective inhibitors of these isoenzymes may add to the therapy of chronic airflow obstruction. However, initial data from clinical trials with selective PDE3 and PDE4 inhibitors have been somewhat disappointing and have tempered the expectations considerably since these drugs had limited efficacy and their use was clinically limited through side effects. The improved understanding of the molecular biology of PDEs enabled the synthesis of novel drugs with an improved risk/benefit ratio. These ‘second generation’ selective drugs have produced more promising clinical results not only for the treatment of bronchial asthma but also for the treatment of chronic obstructive pulmonary disease.
Assessment of antihistamine efficacy and potency
Authors: Howarth
Published: March 2003

H1 antihistamines are widely used in the treatment of conditions such as seasonal and perennial allergic rhinitis, urticaria and angioedema, as well as being an adjunct therapy for anaphylaxis. The development of new compounds within this class of pharmacological agents is based on preclinical and clinical assessments prior to registration. Preclinical assessment of novel compounds has been advanced both by the definition of the molecular structure of the H1 receptor and by high throughput screening, which allows the definition of potent and selective candidate compounds. The elimination, in subsequent evaluations, of those compounds with potential for central nervous system and cardiotoxic effects and those with inappropriate pharmacokinetics restricts the subsequent toxicological and clinical evaluation of novel H1 antihistamines. Clinical evaluation is based initially on human volunteer studies to define pharmacodynamic, pharmacokinetic and safety parameters. Local challenge models such as in the skin or nose for oral therapy or nose and conjunctiva for topical drug development allow definition of potential dose for administration, speed of onset of activity and duration of effect, both in comparison to placebo and to reference compounds. While a range of laboratory allergen challenge models, pollen chamber challenge studies and acute ‘day in the park’ study designs have been used in the early clinical evaluation of H1 antihistaminic activity, ultimately it is the efficacy of novel compounds in naturally occurring disease that is of importance. The assessment of the magnitude and profile of clinical disease improvement in specific disease areas is thus the crucial evaluation. The appropriate selection and characterization of patients, the optimization of the trial design, dependent upon the nature of the disease, and the appropriate selection of endpoints for analysis are thus critical considerations, as well as evaluation of appropriate safety criteria.
The late asthmatic response is associated with baseline allergen‐specific proliferative responsiveness of peripheral T lymphocytes in vitro and serum interleukin‐5
Authors: Van Der Veen  , Van Neerven  , De Jong  , Aalberse  , Jansen  , Van Der Zee
Published: March 2003

Background

Increasing insights into the mechanism underlying the allergen‐induced late asthmatic response (LAR) have been gained with implication of activated eosinophils and CD4+ T lymphocytes. However, the patient characteristics that indicate the individual capacity to develop a LAR are not well‐defined.

Methods

In 22 subjects with mild to moderate house dust mite‐allergic asthma, we investigated the relationship between the LAR and two other models of late‐phase allergic inflammation, i.e. the allergen‐specific proliferative response of peripheral blood T lymphocytes in vitro and the late cutaneous response. Non‐specific bronchial responsiveness (PC20 histamine), lung function (FEV1), peripheral blood eosinophil count, early phase allergic skin sensitivity, and levels of total and specific immunoglobulin E (IgE) were determined prior to bronchial allergen challenge. Serum levels of interleukin‐5 (IL‐5) were measured before and at several time points after allergen inhalation.

Results

A significant correlation was found between the magnitude of the LAR and the allergen‐specific proliferative response of peripheral T lymphocytes (r = 0.44, P = 0.04) but not the late cutaneous response. Stepwise‐multiple linear regression of the magnitude of the LAR on the parameters analysed at baseline, resulted in a model combining PC20 histamine, early phase allergic skin sensitivity, and the allergen‐specific proliferative response of peripheral T lymphocytes (R2 = 0.84, P < 0.001). No contribution of the late cutaneous response to the prediction of the LAR was found. Serum levels of IL‐5 increased significantly at 6 h (P = 0.01) and 24 h (P = 0.003) after bronchial allergen challenge and correlated with the allergen‐specific proliferative response of peripheral T lymphocytes in vitro (ρ = 0.48, P = 0.02).

Conclusions

The findings in this study point to a role of TH2‐lymphocyte responses in the development of the allergen‐induced LAR. In allergic asthmatic patients, allergen‐specific responsiveness of peripheral T‐lymphocytes in vitro may serve as a model to determine the individual capacity to develop a LAR after allergen inhalation.
The effects of carpet fresheners and other additives on the behaviour of indoor allergen assays
Authors: CHEW  , HIGGINS  , MILTON  , BURGE
Published: March 2003

Background

Chemical agents such as tannic acid and detergents have been shown to introduce non‐random bias in allergen measurement.

Objective

We investigated how several substances that are commonly found in floor dust (carpet fresheners, powdered pesticides, and table salt) affected immunoassays of purified standard allergens.

Methods

Three sets of experiments were conducted to: (1) screen for interference with allergen enzyme‐linked immunosorbent assay (ELISA); (2) test for concentration‐response; and (3) assess the site‐of‐action of a given dust additive (i.e. the effect on allergen binding to primary or secondary antibody). The ELISAs are commercially available two‐site monoclonal antibody assays for Der p 1, Der f 1, and Fel d 1, and a monoclonal/polyclonal assay for Bla g 1. Outcomes are reported in terms of reaction rate (colour change per unit time), which is directly proportional to the amount of bound allergen.

Results

In the initial screening experiments, carpet fresheners tended to decrease Der p 1 assay reaction rates, increase Der f 1 assay rates, and produce little change in Fel d 1 assay rates. Three carpet fresheners decreased Der p 1 assay rate responses in a concentration‐dependent manner. Two carpet fresheners noticeably increased Der f 1 assay reaction rates in both the screening and the concentration‐response tests. Powdered pesticides increased reaction rates in the Bla g 1 assays and increased the slope of the dilution curve compared with that of the purified allergen. Salt decreased the reaction rates of Bla g 1 assays at allergen concentrations greater than 0.01 U/mL. For each of the four allergens, the largest effects of dust additives occurred when secondary antibody binding was altered.

Conclusions

Some common household dust components can introduce systematic error into immunoassays for arthropod allergens.
Enhanced basophil histamine release and neutrophil chemotactic activity predispose grain dust‐induced airway obstruction
Authors: PARK  , JUNG  , KANG  , NAHM  , CHO  , KIM
Published: March 2003

Background

The pathogenic mechanism of grain dust (GD)‐induced occupational asthma (OA) remains unclear.

Objective

To understand further the mechanism of GD‐induced OA.

Methods

Fifteen employees working in a same GD industry, complaining of work‐related respiratory symptoms, were enrolled and were divided into two groups according to the GD‐bronchoprovocation test (BPT) result: six positive responders were grouped as group III, nine negative responders as group II and five healthy controls as group I. Serum GD‐specific immunoglobulin (Ig)E (sIgE), specific IgG (sIgG) and specific IgG4 (sIgG4) antibodies were detected by enzyme‐linked immunosorbent assay. Basophil histamine release was measured by the autofluorometric method, and changes of serum neutrophil chemotactic activity were observed by the Boyden chamber method.

Results

For clinical parameters such as degree of airway hyperresponsiveness to methacholine, duration of respiratory symptoms, exposure duration, and prevalences of serum sIgE, sIgG and sIgG4 antibodies, there were no significant differences between group II and III (P > 0.05, respectively). Serum neutrophil chemotactic activity increased significantly at 30 min and decreased at 240 min after the GD‐BPT in group III subjects (P < 0.05, respectively), while no significant changes were noted in group II subjects (P > 0.05). Basophil histamine release induced by GD was significantly higher in group III than those of group I or group II (P < 0.05, respectively), while minimal release of anti‐IgG4 antibodies was noted in all three groups.

Conclusions

These results suggest that enhanced basophil histamine release and serum neutrophil chemotactic activity might contribute to the development of GD‐induced occupational asthma.