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Biomedical subjects

R Sepulveda

Publications and source records attributed to R Sepulveda.

11 recordsLinked to original sources

Combinatorial use of antibodies to secreted mycobacterial proteins in a host immune system-independent test for tuberculosis.

Laboratory diagnosis of tuberculosis is often difficult. Immunodetection of circulating Mycobacterium tuberculosis proteins shed during active infection would not depend on an intact host immune response and could take advantage of the speed and low costs afforded by antibody-based assays. We previously showed that patients with active tuberculosis had increased levels of circulating antigen 85 (Ag85) proteins independent of their tuberculin skin test status (S. I. Bentley-Hibbert, X. Quan, T. Newman, K. Huygen, and H. P. Godfrey, Infect. Immun. 67:581-588, 1999). To extend these observations to a Mycobacterium bovis BCG-vaccinated population and to another secreted mycobacterial protein, Ag85 and PstS-1 (protein antigen B, p38 antigen) were quantified in sera from 97 Chilean tuberculosis patients and healthy controls (many of whom had received BCG as children) using dot immunobinding, mouse monoclonal anti-BCG Ag85 complex antibody, and chicken antipeptide antibodies reactive with M. tuberculosis Ag85B and PstS-1. The latter antibodies had been raised to peptide-derived immunogens expressed on a novel proprietary protein carrier in Escherichia coli. Median serum Ag85 levels measured by using either anti-Ag85 antibody were significantly higher in patients with active tuberculosis than in healthy controls (P, <0.001 to 0.01); the median serum PstS-1 levels were similar in patients and controls. The sensitivity of significantly elevated circulating Ag85 levels in patients with pulmonary tuberculosis measured by anti-Ag85 complex or anti-Ag85B antibodies was 60 and 55%, respectively, but increased to 77% when results obtained with both anti-Ag85 antibodies were considered jointly (P < 0.02). The corresponding specificities for individual and joint consideration were 95, 85, and 80%, respectively. These results indicate that elevated Ag85 levels can be detected in patients with active tuberculosis even after BCG vaccination and suggest that combinatorial use of antibodies directed at different epitopes of this protein could provide a viable strategy for developing new host immune response-independent diagnostic tests for tuberculosis.

Adolescent↗

Medical and surgical treatment of nonallergic asthma associated with gastroesophageal reflux.

Patients presenting to a chest clinic because of adult-onset wheezing with no history of allergy had a 90 percent prevalence of gastroesophageal reflux, even though reflux symptoms were mild or absent. Ninety patients were randomly assigned to receive cimetidine or an identical placebo or to undergo antireflux surgery. During a six-month period, all groups improved clinically; the cimetidine and surgical groups improved more than the placebo group. The intake of pulmonary medication decreased significantly in both cimetidine and surgical groups. Pulmonary function test results improved in the cimetidine- and surgically treated patients; improvement was not statistically significant. At long-term follow-up, the surgical group maintained clinical improvement and decreased pulmonary medication intake, whereas the placebo group worsened. We conclude that gastroesophageal reflux can play a significant role in some patients with nonallergic pulmonary disease and that its treatment can improve pulmonary symptoms and objective measurements of pulmonary function.

Adult↗

Comparison of 1 mg and 5 mg sodium cromoglycate metered dose inhalers in the treatment of asthma: a 12-week double-blind, parallel group trial.

A double-blind, parallel group trial of a 1 mg sodium cromoglycate metered dose inhaler, a 5 mg formulation and a placebo aerosol was undertaken in 139 asthmatic patients with extrinsic allergic asthma. None of the patients had previously been treated with sodium cromoglycate and few (15%) were familiar with the use of a pressurized aerosol device. Each test treatment was taken at a dose of 2 'puffs' 4-times per day for a period of 12 weeks. Response to treatment was assessed by analysis of symptom scores, medication usage and 3-times daily home measurements of PEFR recorded on diary cards, and by assessment of asthma severity and lung function in the clinic at the beginning and end of a 2-week baseline period and at intervals of 3 weeks throughout the trial. Analysis of patient-generated data (symptom scores and PEFR) demonstrated statistically significant differences in favour of each active treatment compared with placebo treatment. Clinic assessments of asthma severity and the investigator's opinion of treatment also showed the superiority of each sodium cromoglycate treatment regimen over placebo. These differences were statistically significant after 9 weeks (high dose) and 12 weeks (both doses). No statistically significant differences were demonstrated between the two active treatment groups in the clinic assessments of asthma severity, or in the home or clinic measurements of PEFR. There was, however, a consistent trend in favour of the higher dose formulation with respect to diary card symptom scores. In general, improvement in the low-dose sodium cromoglycate treatment group was slower than in the high-dose group suggesting an advantage for the 5 mg sodium cromoglycate inhaler in terms of onset of therapeutic response. The results indicate that sodium cromoglycate administered by pressurized aerosol at a dose of 2 x 1 mg or 2 x 5 mg 4-times daily is effective in the treatment of asthma and suggest that the higher dose formulation may provide more rapid control of symptoms.

Administration, Inhalation↗

Chemonucleolysis failures treated by PLIF.

Chemonucleolysis is a procedure in which an enzyme is injected into the intervertebral disc for the purpose of alleviating sciatic pain. This has a reported success rate of 70%-90%. Of the failures, several will benefit from a classic lumbar laminectomy for removal of a free fragment in the spinal canal caused by either improper technique or inadequate enzyme activity. However, in a significant number of cases, the failure is related to either instability or the compression of the nerve roots in the neural foramen. Observations on 17 cases demonstrate that PLIF can relieve pain and other symptoms in cases of failed chemonucleolysis.

Adult↗

Enzyme linked immunosorbent assay (ELISA) for IgG and IgE antibodies to protein and polysaccharide antigens of Aspergillus fumigatus.

ELISA has emerged as a useful alternative to other more costly and complex tests. Polystyrene microhaemagglutination plates have been used as solid phase to absorb Aspergillus fumigatus protein and polysaccharide components for detection of specific antibodies in patients with various forms of pulmonary aspergillosis. IgG and IgE antibodies to the polysaccharide as well as the protein allergens have been found. For the IgE test a double antibody technique has been developed, which is more sensitive than the conventional indirect ELISA.

Antigens, Fungal↗

Asthma and extrinsic allergic alveolitis due to Merulius lacrymans.

A teacher with breathlessness of insidious onset developed acute symptoms on return home following his discharge from hospital. His flat was found to have extensive dry rot (Merulius lacrymans). Precipitins and specific IgE and IgG antibody against M. lacrymans were present and intracutaneous testing gave a typical dual skin reaction. Pulmonary physiology demonstrated airflow obstruction with a low DLCO and KCO, and a chest X-ray showed diffuse micronodular shadowing, maximal in the mid-zones. Inhalation challenge testing provoked a combined asthmatic reaction without a change in DLCO. Rapid clinical recovery and more gradual radiographic and physiological improvement followed cessation of exposure to the antigen.

Adult↗

The acceptability, safety and efficacy of nedocromil sodium in long-term clinical use in patients with perennial asthma.

The safety, acceptability and efficacy of nedocromil sodium, given by metered dose inhaler at a dosage of 4 mg four times daily, were investigated in a 52-week open assessment study of 79 perennial bronchial asthmatic patients maintained on oral bronchodilator therapy. Extensive laboratory monitoring of renal, hepatic and haematological functions before, during and at the end of the study failed to provide any evidence of drug-induced toxic effects. Nedocromil sodium was well tolerated with no serious adverse effects reported. Nineteen patients were withdrawn from the study, two complaining of sore throats and one of severe cough after nearly 1 year of treatment. The remainder were withdrawn because of intolerance to theophylline (one patient), non-cooperation (three), relocation outside the trial area (seven), onset of uncontrolled asthma (two) and pregnancy (three patients). Although this was an open assessment study, analysis of the diary card measurements and clinic assessments indicated that nedocromil sodium is an effective long-term therapy in the maintenance treatment of bronchial asthma.

Adolescent↗