PubMed Health⌕ Search

Biomedical subjects

B H Davies

Publications and source records attributed to B H Davies.

At least 19 recordsLinked to original sources

Human leucocyte antigen polymorphisms in nut-allergic patients in South Wales.

BACKGROUND: Peanuts and tree nuts are among the most common foods provoking severe allergic reactions including fatal anaphylaxis. However, little is known of the underlying genetic and immunological mechanisms involved. OBJECTIVE: Based on findings in other allergic diseases, we have investigated whether specific human leucocyte antigens (HLA) are associated with nut allergy. METHOD: Eighty-four patients presenting at the allergy clinic with symptoms of nut allergy were typed for the HLA Class I (HLA-A and B) and Class II (HLA-DRB1 and DQB1) loci by PCR using sequence-specific primers. Carriage frequencies were compared with 82 atopic non-nut-allergic subjects and 1798 random blood donors. RESULTS: The frequency of HLA-B(*)07 (28.57%) and DRB1(*)11 (15.48%) was increased in the nut-allergic patients compared to the atopic controls (12.20% and 3.66%, respectively) but not when compared to the blood donors (28.86% and 10.12%). DRB1(*)13 and DQB1(*)06 were both increased in frequency in the nut allergy patients over both the atopic and blood donor controls. However, none of these increased frequencies were significant when corrected for the number of comparisons undertaken. CONCLUSION: At HLA '2-digit resolution' and with undifferentiated patients with nut allergy, there are no major disturbances in the frequency of HLA-A, B, DRB1 or DQB1 types. However, the difference in frequency of HLA-DRB1(*)11 between the nut allergy patients and the atopic controls merits further investigation as this may represent an important phenotypic relationship.

Adolescent↗

Polymorphism in the STAT6 gene encodes risk for nut allergy.

Nut allergy is an important and potentially life threatening food allergy with a prevalence of one in 150 children in the UK population. STAT6 (signal transducer and activator of transcription) is an important molecule in the induction and regulation of an allergic response, which maps to chromosome 12q in a region previously linked with total serum IgE concentration and atopy in different populations. We have examined the frequency of a single nucleotide polymorphism (SNP) in the 3'UTR region of STAT6 gene in 71 UK Caucasoid patients diagnosed with nut allergy and 45 atopic patients without nut allergy using PCR-RFLP and compared these with 184 UK healthy controls. The STAT6 G allele frequency was significantly increased in nut allergy patients compared with blood donor controls (P < 0.0001, OR = 2.9, 95% CI: 1.7-4.9), which was under a recessive model (GG vs GA+AA, P = 0.0001, OR = 3.2, 95% CI: 1.7-5.8) but not in atopic patients without nut allergy. The G allele was most frequent in the severe cases and GG homozygosity was associated with the increased risk of severe reaction (OR = 3.9, 95% CI: 1.9-8.3). We conclude that STAT6 3'UTR polymorphism is associated with susceptibility and severity in nut allergic patients in our population.

Child↗

Seasonal variation in interleukin 4 in patients with hayfever.

This study was performed to investigate the value of interleukin 4 as a marker of activity in mild atopic disease. We compared IL-4 levels to eosinophil cationic protein (ECP), a suggested inflammatory marker in allergic disease, in patients with hayfever. Patients with hayfever were assessed during January and then in late June at the height of the grass pollen season, and their levels of serum ECP and IL-4 compared. Serum ECP was determined by radio-immunoassay and serum IL-4 by a high-sensitivity enzyme-linked immunosorbent assay. ECP was found to increase significantly in patients with hayfever during the grass pollen season (P<0.01). Conversely, serum levels of IL-4 were found to decrease significantly over the same period when compared with winter values. ECP and IL-4 were not seen to correlate significantly with each other. The fall in serum IL-4 seen during the grass pollen season in the hayfever patients may reflect allergen driven upregulation of membrane IL-4 receptor expression or sequestration of cytokine producing cells to inflammatory sites. These findings suggest that serum IL-4 is a poor indicator of inflammatory status in allergic disease.

Blood Proteins↗

A confidential inquiry into asthma deaths in Wales.

BACKGROUND: Death from asthma is regarded as preventable in principle, especially under the age of 65 years. METHODS: In 1994 a confidential inquiry was set up to investigate deaths attributable to asthma in residents of Wales under the age of 65 years. During the period of the inquiry 92 cases were notified as being ascribed to asthma, or (in 1996) having a mention of asthma on the death certificate. Of these, 80 were investigated further with the help of general practitioners, hospital notes, and relatives. The details were then considered by a small panel of doctors who endeavoured to identify factors that may have contributed to the deaths. RESULTS: Asthma was considered to be the underlying cause of 52 deaths. Although disease severity was usually a major factor, some aspect of the patient's behaviour or circumstances seemed to have contributed to 31 deaths, while in 15 cases there was probably a deficiency in medical care. CONCLUSIONS: Some preventable asthma deaths still occur, particularly in relation to inadequate treatment. Factors associated with patients' behaviour and circumstances are more difficult to tackle but, if doctors are aware of high risk patients, increased vigilance may prevent some deaths.

Adolescent↗

The assay of interleukin 4 in the serum of normal subjects and atopic patients using a novel immunoassay.

Interleukin 4 (IL-4) was measured in the serum of normals and mild atopic patients using a high sensitivity ELISA system involving an amplification stage. The method was found to have a limit of detection of 0.02 pg/ml after a square root transformation of the concentration data and to show good reproducibility with coefficients of variation between 11 and 14%. Recoveries of standard IL-4 from serum was greater than 90%. Markedly elevated levels of IL-4 were seen in the atopic groups compared with the normals. No association was found between total white cell counts, lymphocyte or eosinophil counts and serum IL-4 levels. This study demonstrates that serum IL-4 levels can distinguish between atopic subjects and normals, even in mild or symptomless disease. This may prove valuable in the management of atopic disorders.

Adolescent↗

Interleukin-8. Differential expression in lone fibrosing alveolitis and systemic sclerosis.

Fibrosing alveolitis may occur alone (CFA) or in association with systemic sclerosis (FASSc). FASSc was recently shown to have a prognostic advantage over CFA. Because interleukin-8 (IL-8) is likely to be a major determinant of neutrophil alveolitis, we evaluated IL-8 expression in patients with CFA and FASSc and compared it with that in normal individuals and sarcoidosis and systemic sclerosis patients without pulmonary involvement (SSc no FA). IL-8 protein in bronchoalveolar lavage fluid (BALF) was assessed by immunoassay, and IL-8 mRNA expression was assessed using Northern analysis and reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization of lung parenchyma. Compared with normal subjects, IL-8 concentration was significantly greater in both CFA (p < 0.001) and FASSc groups (p < 0.05) but no different in sarcoidosis. The IL-8 concentration in CFA was higher than in FASSc (p < 0.01) and was related to BAL % neutrophils (rs = 0.48, p < 0.01). IL-8 mRNA expression evaluated by Northern analysis was seen only in patients with CFA and FASSc and was related to BAL % neutrophils (rs = 0.63, p < 0.01). We suggest that IL-8 is a key factor in the pathogenesis of fibrosing alveolitis and that the poorer prognosis of CFA compared with FASSc is related to higher levels of IL-8 within the lower respiratory tract.

Adult↗

Salivary PAF in acute myocardial infarction and angina: changes during hospital treatment and relationship to cardiac enzymes.

Salivary levels of platelet activating factor (PAF) were measured together with serum CPK and interleukin 2 receptor in 30 patients admitted to the coronary care unit, 9 patients with pulmonary tuberculosis, 10 with acute severe asthma and 8 normal controls. 16 of the 30 C.C.U. patients had sustained a acute myocardial infarction (M.I.) 5 had acute angina and the remaining 9 had non cardiac chest pain. Salivary PAF on admission was significantly higher in the M.I. Patients than in the normal subjects, asthmatics, tuberculosis patients and those with non cardiac chest pain (p < 0.001 in all cases) but not those with angina. After 48 hours PAF levels fell in the subjects with M.I. (p < 0.01) and no significant difference was seen between any group. PAF levels did not show any relationship with CPK levels or site of infarct in the M.I. patients. Interleukin 2 receptor was not significantly raised in the M.I. group as a whole but some individual patients showed markedly increased serum levels, but these levels did not correlate with either salivary PAF or serum CPK.

Angina Pectoris↗

Diffuse pulmonary fibrosis and the Hermansky-Pudlak syndrome: clinical course and postmortem findings.

The Hermansky-Pudlak syndrome consists of albinism, platelet function defect, pigment laden macrophases and, on occasions, pulmonary fibrosis. The clinical course and postmortem findings of a patient with pulmonary fibrosis which mimicked cryptogenic fibrosing alveolitis are reported. Histological examination revealed a chronic inflammatory infiltrate of pigment laden microphages.

Adult↗

A bronchial butterfly.

We report on an asthmatic patient who accidentally inhaled the small metal backing ("butterfly") of a nose stud, which she wore daily. Despite administration of nebulized salbutamol, postural drainage, and the use of rigid and fibreoptic bronchoscopes, attempted removal of the butterfly remained unsuccessful. Spontaneous expulsion of the butterfly occurred two months following inhalation. We suggest that consideration should be given by nose stud jewelry manufacturers to a more secure fixing device.

Adult↗

Topical levocabastine is more effective than sodium cromoglycate for the prophylaxis and treatment of seasonal allergic conjunctivitis.

The efficacy, tolerability, and adverse-effect profile of the recently developed, topical antihistamine levocabastine were compared with those of sodium cromoglycate in a 4-week double-blind, placebo-controlled trial in 95 patients with seasonal allergic conjunctivitis. At the end of the trial, global therapeutic efficacy was considered to be excellent or good in 87% of levocabastine-treated patients, as compared with 68% of sodium cromoglycate-treated patients (P = 0.006) and 63% of those who received placebo (P = 0.05). After 4 weeks of treatment, levocabastine patients had experienced significantly greater relief from their most severe ocular symptom than patients in the sodium cromoglycate group (P < 0.05). Furthermore, 37% of levocabastine-treated patients were virtually symptom-free for at least 75% of the treatment period, as compared with only 6% of patients in the sodium cromoglycate group (P < 0.01) and 4% of those who received placebo (P < 0.01). Moreover, this trend was maintained on days when the pollen count was high, when the corresponding figures were 33%, 6% (P = 0.02), and 4% (P = 0.02), respectively. Levocabastine was well tolerated. Indeed, the incidence of adverse reactions was no greater in the levocabastine group than in the placebo group. Topical levocabastine is an effective and well-tolerated drug for the prophylaxis and treatment of seasonal allergic conjunctivitis.

Administration, Topical↗

Inhalation challenge in pigeon breeder's disease: BAL fluid changes after 6 hours.

The purpose of this study was to determine the cellular events occurring 6 h after bronchial inhalation challenge, in a group of pigeon breeders. Twelve subjects agreed to undergo challenge, either with nebulized pigeon serum (Ps) (n = 10), or with saline (n = 2). The development of characteristic symptoms was used to detect a positive response in combination with monitoring tests (white blood cell count (WBC), body temperature, and spirometry). An initial bronchoalveolar lavage (BAL) was performed before inhalation challenge, and a further BAL on the previously spared right middle lobe subsegment or lingula 6 h after challenge. Paired bronchoalveolar lavage fluid (BALF) samples were analysed for urea, albumin, total and differential WBC, interleukin-1 and interleukin-2. There was a significant increase in total cells, lymphocytes, T-lymphocytes, and neutrophils; numbers.ml-1 of BALF in responders. A monitoring score reflecting severity of patient response correlated with an increase in all cell types (p < 0.05). In conclusion, responders developed both a BALF lymphocytic and neutrophilic "alveolitis" following inhalation challenge, the degree of BALF "alveolitis" correlating with the severity of patient response.

Adult↗

Massive pleural effusion: an unusual presentation of Castleman's disease.

Giant lymph node hyperplasia (Castleman's Disease) is a rare cause of pleural effusion. We report the case of a 51 yr old West Indian male, who presented with a recurrent massive pleural effusion, due to a tumour arising from the pleura. He underwent parietal pleurectomy and subtotal excision of the tumour. Histological analysis of the specimen showed the features of multicentric Castleman's disease. Nine months following surgery he remains well, with no recurrence of the effusion.

Castleman Disease↗

Pigeon breeders' lung--the effect of loft litter materials on airborne particles and antigens.

An Andersen sampler was used to collect different sized fractions of airborne dust within pigeon lofts. Antigens associated with pigeon breeders' lung were then measured using an ELISA technique. Levels of soluble antigen in the 0.5-5 microns range correlated significantly with airborne particle concentrations in the same range, determined by particle size analysis. However, antigenic material was not soley confined to the 0.5-5 microns fraction and was detected in particles up to 11 microns in diameter. Using both particle size analysis and ELISA in local pigeon lofts revealed significantly increased particles (up to x 50) and antigens (up to x 10) in some lofts employing litter materials to dehydrate voided pigeon droppings, compared with lofts cleaned regularly with no litter agent. Paradoxically, ventilation did not influence particle or antigen concentrations under static conditions or during loft cleaning. The settling rate of loft dusts correlated significantly with that of the litter used, suggesting litter particles were a carrier for soluble pigeon dropping components, but differences in particle numbers generated from the litters and litter/dropping combinations showed that an interaction between voided droppings and litter agents had occurred. A change from litter systems to regular cleaning was undertaken in two lofts, resulting in a marked decrease in respirable particles and antigens.

Air Pollutants↗

Measurement of interleukin-6 in bronchoalveolar lavage fluid by radioimmunoassay: differences between patients with interstitial lung disease and control subjects.

Bronchoalveolar lavage fluid (BALF) from subjects with a variety of interstitial lung diseases (active sarcoidosis, pigeon breeders' disease (PBD), asymptomatic pigeon breeders, patients with idiopathic pulmonary fibrosis) and from control subjects were assayed for interleukin-6 (IL-6) using a novel radioimmunoassay system. IL-6 was detectable in BALF from all groups, with disease groups showing significantly increased IL-6 levels compared with controls (P less than 0.01 in all cases). When these results were standardized, using urea to compensate for dilution effects in the BALF, only the asymptomatic pigeon breeders had significantly higher IL-6 levels than the controls (P less than 0.025), with all other groups showing no difference. When albumin was used for standardization, both the PBD group (P less than 0.001) and the sarcoidosis patients (P less than 0.01) had considerably lower levels of IL-6 than the control subjects. Using either albumin or urea for standardization, the PBD patients had significantly lower levels of IL-6 than do their asymptomatic counterparts (P less than 0.001 in both cases). This is contrasted by the finding of greatly elevated levels of IgG in the BALF of the PBD patients compared with asymptomatics (P less than 0.001). There was, however, no relation between IL-6 and IgG in any patient group, although the PBD patients had the lowest IL-6 and highest IgG as a group. These findings may suggest a mechanism by which asymptomatic subjects remain free from clinical complaints.

Albumins↗

Immunoglobulin and antibody levels in bronchoalveolar lavage fluid from symptomatic and asymptomatic pigeon breeders.

Twenty-one symptomatic subjects with pigeon breeders' lung (PBL) and 10 asymptomatic pigeon breeders, with a similar exposure to pigeon antigens, underwent bronchoalveolar lavage. Total IgG, IgM and IgA in lavage fluid were determined as were specific antibody levels against antigens in pigeon serum and droppings. Results were converted to levels in epithelial lining fluid (ELF) using lavage and serum urea ratios. It was found that symptomatics represent a group that is hyperreactive to pigeon antigens compared with the asymptomatic group with significantly higher IgG, IgM, IgA levels as well as specific antibody levels against pigeon serum and droppings. Paired serum and ELF samples from 12 symptomatic subjects showed significantly elevated IgG, IgM and IgA levels in ELF compared with serum when values were expressed in terms of albumin. This strongly supports the concept of local production of immunoglobulins within the lung after inhaling immunogens as opposed to their diffusion from the vasculature. Results for IgA indicate that any putative protective role for this immunoglobulin is not valid in relation to the prevention of extrinsic allergic alveolitis. Analysis of smoking habits, lung immunoglobulins and response to inhalation challenge confirm the negative influence of smoking on total and functional lung immunoglobulins; however, levels in the ELF of ex-smokers suggest that the effect of smoking is not permanent. Smoking did not prevent responses to inhalation challenge.

Allergens↗