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Biomedical subjects

C Teale

Publications and source records attributed to C Teale.

36 records · Page 2Linked to original sources
PubMed1992

Simplifying the assessment of patients with chronic airflow limitation for home nebulizer therapy.

One-hundred nebulizer trials were performed in 98 adult patients with chronic airflow limitation who had remained symptomatic despite regular use of bronchodilators by metered dose or dry powder inhalation. Mean baseline FEV1 was 0.9 (SD = 0.41) 1, FVC -2.0 (0.74) 1 and PEFR 169 (77) 1 min-1. After laboratory measurements of reversibility to inhaled salbutamol (5 mg) and ipratropium bromide (0.5 mg), patients were supplied with a compressor and a peak flow meter to make twice daily measurements at home for 3 weeks. They nebulized normal saline, salbutamol (5 mg) and salbutamol (5 mg) ipratropium (0.5 mg) mixture 6-hourly, each for 1 week. A positive nebulizer trial was defined as a 15% increase in mean PEFR over a week on an active treatment compared to the week on saline. Twenty-eight patients had positive trials based on these criteria. Of these nine responded to both active treatments and 16 to the salbutamol/ipratropium mixture. Although no laboratory measurements predicted a positive domiciliary trial, the patients' subjective assessment of benefit had a 93% sensitivity and 87% negative predictive value. We conclude that an appropriate protocol for assessing the value of long-term nebulized bronchodilators is for patients to measure their PEFR during a week of nebulized saline and a week of nebulized beta-agonist/ipratropium mixture. Those with an increase of 15% in mean PEFR in the week on active treatment and who experienced subjective benefit should be supplied with a compressor. Had we conducted our 100 trials in this way we would have started 25 of our 98 patients on long-term home nebulized bronchodilators.

Adult↗
PubMed1991

The nature and importance of the inter-epsilon chain disulfide bonds in human IgE.

IgE antibodies are best known for their pathological role in allergy. The class-specific effector sites are located in the epsilon chains; these form covalent dimers via two cystine residues (Cys241 and Cys328) linking opposite C epsilon 2 domains. The nature and biological significance of the inter-epsilon chain disulfide-bond arrangement is unresolved. For structural and functional analysis site-specific mutations were introduced into the C epsilon 2 domain of recombinant human IgE. The introduction of an additional cyanogen bromide cleavage site (His246----Met) facilitated the identification of parallel disulfide bond pairing. This linkage was also confirmed for myeloma IgE PS by sequence determination of disulfide-linked C epsilon 2 dimers. Substitution of Cys241 and Cys328 by Ser does not destroy receptor binding, but reductive alkylation, or the replacement of Cys328 by Met, leads to loss of activity. This shows that covalent dimerization is not essential for IgE/receptor interaction and points to the importance of the structural integrity of the site surrounding Cys328, visualized in a new model of human Fc epsilon.

Amino Acid Sequence↗
PubMed1991

Outbreak of tuberculosis in a poor urban community.

A woman from a poor urban community presented recently with pulmonary tuberculosis. Screening of contacts revealed 10 cases of tuberculosis, eight of whom were children. A further 10 children had grade 2-3 positive Heaf tests and were given chemoprophylaxis. Tuberculosis remains a potential problem, particularly in young unimmunized children in deprived areas.

Adolescent↗
PubMed1991

Reversibility tests in chronic obstructive airways disease: their predictive value with reference to benefit from domiciliary nebuliser therapy.

The role of short-term tests of reversibility in selecting patients with COAD for long-term nebuliser therapy is uncertain. In a double-blind placebo-controlled crossover study we have examined the correlation between short-term reversibility and response to a home nebuliser. We studied 20 patients with severe COAD (mean age 66, mean FEV1 0.81 l) and little reversibility (less than 20% increase in FEV1 post-inhaled salbutamol 200 micrograms and less than 25% increase in peak expiratory flow rate, PEFR, on oral steroids). PEFR, spirometry, lung volumes and airways conductance were recorded before and 1 h after a mixture of nebulised ipratropium 0.5 mg and fenoterol 1.25 mg. Patients then recorded twice-daily PEFR at home while they received nebulised ipratropium plus fenoterol, or saline placebo, four times a day for three week blocks using a double-blind cross over protocol. Mean PEFR on home nebuliser rose from 164 l m-1 (placebo) to 196 l m-1 (ipratropium plus fenoterol), paired t-test P = 0.0001. Correlation coefficients between short-term response for PEFR, spirometry and lung volumes, and improvement in home PEFR on nebulised ipratropium plus fenoterol, were all poor (R = -0.37-0.35, P = 0.83-0.11). We conclude that in severe COAD, reversibility tests of PEFR, spirometry and lung volumes do not correlate with response to a home nebuliser. Home measurements of PEFR are probably the best objective method of assessing response to a home nebuliser in such patients.

Aged↗
PubMed1991

Time of development of tuberculosis in contacts.

The British Thoracic Association has recommended that close contacts of smear-positive cases of tuberculosis be followed up for at least 2 yrs (Tubercle 1978; 59: 245-259) but Selby et al. have recently suggested that a reduction in duration of follow up may be appropriate (Respir Med 1989; 83: 353-355). We have reviewed the results of contact procedures in Leeds to determine whether our experience supports reduction in the duration of follow up of contacts of patients with tuberculosis. In the 5-yr period 1983-87 there were 555 cases of tuberculosis (135 in Asians) of whom 42 (7.6%) were identified by contact procedures. In addition, contact procedures identified 35 children who were given chemoprophylaxis for positive Heaf tests (grade 2 or more). Of the 42 contacts with tuberculosis, 30 (71%) were diagnosed at the first visit, eight (19%) were diagnosed 6 months later and four (10%) were diagnosed 16-24 months after their initial clinic attendance. Five of the 42 contacts with TB were Asian, two of whom were diagnosed late. Seven out of ten non-Asian contacts who were diagnosed late had initial Heaf reactions of grade 1 or 2. All cases diagnosed late were contacts of a sputum-positive source. Poverty, as defined by residence in the Leeds Urban Priority Area, was associated with an increased risk of 3.3-fold for tuberculosis and a sixfold risk for chemoprophylaxis diagnosed by contact procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Effects of H1-receptor blockade with terfenadine in nocturnal asthma.

1. In a single-blind placebo controlled study we have measured peak flow (PEFR) at 04.00 h and 16.00 h in eight asthmatics 6 h after placebo or terfenadine 120 mg, to determine if diurnal variation in histamine mediated effects contribute to nocturnal bronchoconstriction in asthma. 2. On placebo there was a significant diurnal variation in mean PEFR of 41 l min-1 (P less than 0.05). Terfenadine improved 04.00 h baseline mean PEFR from 242 to 278 l min-1 (P less than 0.05) but a 38 l min-1 diurnal variation in mean PEFR persisted (P less than 0.05). 3. We conclude that H1-receptor blockade with terfenadine may produce modest nocturnal bronchodilatation but does not influence the diurnal variation in PEFR in asthma suggesting that H1-receptor mediated effects are not important in the pathogenesis of nocturnal asthma.

Adult↗
PubMed1991

Regular nebulised terbutaline in chronic obstructive airways disease: dose-response studies fail to detect tolerance.

1. To determine the effects of high dose terbutaline on the possible development of tolerance we have examined the influence on dose-response of regular nebulised terbutaline. 2. We studied 10 subjects with severe chronic obstructive airways disease (COAD), mean age 63 years mean (s.e. mean) PEFR 142 l min-1 (19), FEV1 0.77 1 (0.12) and FVC 1.93 (0.19). Cumulative dose-response curves were measured (PEFR, FEV1 and FVC) to six incremental doses of terbutaline (0.5-8 mg) before and 1, 4, 8 and 12 weeks after starting nebulised terbutaline 5 mg four times a day. 3. Maximal bronchodilatation (Emax) was calculated by polynomial regression. Responses were examined by analysis of variance. 4. Mean baseline PEFR increased by 32 l min-1 (P less than 0.05), FEV1 by 0.16 1 (NS) and FVC by 0.54 l (P less than 0.05) after 12 weeks. Initial mean Emax PEFR was maintained throughout the study. The percentage of mean Emax PEFR achieved by each cumulative dose of terbutaline either increased (0.5 mg, 1 mg and 2 mg, P less than 0.01) or was maintained (4 mg, 6 mg and 8 mg) throughout the study. 5. We conclude that in severe COAD regular nebulised terbutaline 5 mg four times a day produces a sustained improvement in baseline lung function without changes in dose-response which would suggest tolerance.

Adult↗
PubMed1991

Dose response to inhaled salbutamol in chronic obstructive airways disease.

High dose inhaled salbutamol is increasingly used in the management of chronic obstructive airways disease. To determine the range of doses to achieve optimal bronchodilatation and the proportion of patients requiring high dose therapy we have studied 23 patients with chronic obstructive airways disease. Cumulative dose responses were measured to six incremental doses of salbutamol (0.2 to 1.2 mg) delivered by metered dose inhaler. Results were analysed by polynomial regression to calculate the smallest dose required to produce 90% maximal bronchodilatation in each patient. While 5/23 (22%) required greater than 1 mg the majority, 14/23 (61%), achieved 90% maximal bronchodilation with salbutamol 0.6 mg or less. The 8 patients with severe airflow limitation (FEV1 less than or equal to 1 litre) showed a similar pattern of response. We conclude that in chronic obstructive airways disease there are wide individual variations in the dose of inhaled salbutamol producing 90% maximal bronchodilatation with only a minority requiring high dose therapy.

Administration, Inhalation↗
PubMed1990

Adrenaline and nocturnal asthma.

OBJECTIVE: To determine whether the nocturnal fall in plasma adrenaline is a cause of nocturnal asthma. DESIGN: Double blind placebo controlled cross-over study. In the first experiment the nocturnal fall in plasma adrenaline at 4 am was corrected in 10 asthmatic subjects with an infusion of adrenaline after parasympathetic blockade with 30 micrograms/kg intravenous atropine. In the second experiment 11 asthmatic subjects showing similar variations in peak expiratory flow rate had the nocturnal fall in plasma adrenaline corrected by infusion before atropine was given. PATIENTS: Asthmatic subjects with a diurnal variation in home peak expiratory flow rate of greater than 20% for at least 75% of the time in the two weeks before the study. MAIN OUTCOME MEASURES: Peak expiratory flow rate and plasma adrenaline. RESULTS: Correction of the nocturnal fall in plasma adrenaline at 4 am to resting 4 pm levels did not alter peak expiratory flow rate either before or after parasympathetic blockade with atropine. CONCLUSION: A nighttime fall in plasma adrenaline is not a cause of nocturnal asthma.

Adult↗
PubMed1990

Construction, function and immunogenicity of recombinant monoclonal antibodies.

Much of the interest in chimaeric antibodies stems from their presumed lack of immunogenicity in humans. We have tested this assumption using mouse models and have concluded that whilst chimaerisation can certainly lead to a reduction in the total anti-antibody response, a substantial anti-variable region response can nevertheless remain. As it therefore seems likely that determinants within the variable region lead to this anti-antibody response, we have initiated experiments to test whether it might be possible to use transgenic mice that carry human immunoglobulin gene segments in their germline configuration as a means of making a repertoire of entirely human antibodies.

Animals↗
PubMed1989

A matched set of rat/mouse chimeric antibodies. Identification and biological properties of rat H chain constant regions mu, gamma 1, gamma 2a, gamma 2b, gamma 2c, epsilon, and alpha.

Rat C regions mu, gamma 1, gamma 2a, gamma 2b, gamma 2c, epsilon, and alpha have been characterized by means of chimeric antibody technology. A set of rat/mouse Ag-specific (anti-4-hydroxy-3-nitrophenacetyl) antibodies was constructed that differ only in the H chain constant region but carry identical V region and L chain, both of which are of mouse origin. All rat constant regions could be expressed and m.w. were as expected from the protein sequence. A slight variation in mobility within the IgG subclasses allowed us to establish a hierarchy for the sizes of the four gamma H chains; gamma 2b greater than gamma 1 greater than gamma 2c greater than gamma 2a. Rat IgG2c and IgG2b could be purified on both protein A and protein G while rat IgG2a could only be purified on protein G. Rat IgM and IgG2b were the most potent in C-mediated hemolysis. This was not simply a consequence of the amount of C1q bound because IgG2c bound C1q efficiently but was relatively poor in cell lysis. In ADCC using human effector and target cells, IgG2b and IgG1 were the most effective.

Animals↗
PubMed1989

Hepatitis B markers in West Yorkshire firemen.

Firemen have been considered at occupational risk of hepatitis (HBV) infection, but proof is lacking. The aim of this study was to assess the degree of risk by determining the prevalence of serological markers of past infection with HBV in members of the West Yorkshire Fire Service. Sera from 173 firemen, 9.3% of the brigade, were tested for antibodies to HBV surface antigen and to core antigen. Those containing anti-HBs greater than or equal to 10 IU/L or anti-core antibody, were also tested for antibody to HBe antigen. The presence of more than one marker was used to define past infection. One sample satisfied this criterion, giving a prevalence rate of 0.6%. This compares with a rate of 1% in London blood donors. We conclude that the group shows no evidence of having been at increased risk of HBV infection. A comprehensive vaccination policy for firemen might be questionable.

Adult↗
PubMed1989

A repertoire of monoclonal antibodies with human heavy chains from transgenic mice.

The introduction of human immunoglobulin gene segments in their unrearranged configuration into the germ line of mice might allow the production of a repertoire of human antibodies. Such transgenic mice could be used for the production of human monoclonal antibodies against human antigens. To test the feasibility of this approach, mice were created that carry a human heavy-chain minilocus comprising unrearranged immunoglobulin variable, diversity, and joining elements linked to a human mu-chain gene. The gene segments of this minilocus are rearranged in a large proportion of cells in thymus and spleen but not in nonlymphoid tissue. Some 4% of the B lymphocytes synthesize human mu chains resulting in a serum titer of about 50 micrograms of transgenic IgM antibody per ml. Hybridomas were established from the transgenic mice that stably secreted several micrograms of antibodies containing human mu heavy chains per milliliter.

Animals↗
PubMed1989

Calcification on chest radiographs: the association with age.

Seven hundred chest radiographs taken in a general hospital were reviewed, 100 (50 men and 50 women) from each of seven decades (3rd to 9th). Each radiograph was examined to determine the site and extent of calcific changes. Prevalence of costal cartilage calcification increased from 6% in the 3rd decade to 45% in the 9th and was commoner in men. Aortic calcification was absent below age 50 and increased from 4% in the 6th decade to 57% in the 9th. Both these trends were statistically significant. Other sites of calcification were found only in patients aged over 70; these included pleural, pericardial, tracheal, myocardial and diaphragmatic calcification.

Adult↗