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Biomedical subjects

D M Geddes

Publications and source records attributed to D M Geddes.

232 records · Page 13Linked to original sources
PubMed1977

alpha 1-antitrypsin phenotypes in fibrosing alveolitis and rheumatoid arthritis.

alpha 1-antitrypsin (alpha 1-A.T.) phenotypes were determined in 55 patients with rheumatoid arthritis (R.A.), 33 patients with R.A. and either obstructive airways disease or recurrent chest infections, 49 patients with fibrosing alveolitis (F.A.), 22 patients with R.A. and F.A., and 200 healthy controls. A highly significant increase in the frequency of MZ phenotype was found among patients with F.A., both with and without R.A. Patients with R.A. alone had a normal distribution of phenotypes. Inherited modification of immune function may predispose to F.A. Alternatively, lowered levels of alpha 1-A.T. associated with non-M phenotypes may predispose to tissue damage with subsequent fibrosis.

Alleles↗
PubMed1977

Ornithosis pneumonia associated with haemolysis.

The case of a patient with ornithosis pneumonia associated with a haemolytic anaemia is described. The infection responded to oxytetracycline and the anaemia subsequently resolved.

Anemia, Hemolytic↗
PubMed1977

The effect of isoprenaline on plasma renin activity in man: a dose-response curve.

Four normal subjects on a free sodium intake received intravenous isoprenaline in doses of 2, 4, 8 and 16 microgram over 2 min. Three of the subjects received a second infusion of 8 microgram. The rate of renin release indexed by changes in plasma renin activity increased in all subjects at each dose level. The mean peak levels of plasma renin were 9%, 29% and 77% above the mean control levels at doses of 2, 4 and 8 microgram respectively. The response of 16 microgram was no different from that seen with 8 microgram. The renin response obtained at 8 microgram was highly reproducible such that the coefficient of variation for duplicate estimations of plasma renin (twelve duplicates) ranged from 1.7 to 4%.

Dose-Response Relationship, Drug↗
PubMed1977

Progressive airway obliteration in adults and its association with rheumatoid disease.

Six patients with rapidly progressive airway obliteration in the absence of chronic bronchitis or emphysema are reported. Because this pattern of lung disease is very uncommon and five of the six patients had classical rheumatoid arthritis an association between the two diseases is suggested. The patients presented with rapidly developing breathlessness, and râles and a high-pitched mid-inspiratory squeak were heard over the lung fields. Chest radiographs showed distended lungs but were otherwise normal. Tests of lung fuction showed airflow obstruction, most marked at low lung volumes, with air trapping. The carbon monoxide gas transfer coefficient, maximum static recoil pressure and static compliance were normal. In spite of treatment with antibiotics, bronchodilators and corticosteroids, five died in respiratory failure five to 18 months after first becoming breathless. Post-mortem examination in four patients showed an obliterative bronchiolitis but no mucous gland hypertrophy or significant emphysema.

Adult↗
PubMed1976

Effect of nitrazepam and flurazepam on the ventilatory response to carbon dioxide.

Ventilatory response to CO2 was measured before and after two different benzodiazepine hypnotics in both chronic bronchitics and patients without chest disease. Flurazepam, but not nitrazepam, produced a significant decrease in CO2 sensitivity, although there was no significant change in FEV1 or mixed venous PCO2. This is the first unequivocal evidence of central depression of respiration by a benzodiazepine and may be the mechanism by which benzodiazepines cause deterioration in patients with respiratory failure.

Adolescent↗
PubMedDate not supplied

Gene therapy for cystic fibrosis.

Cystic fibrosis (CF) is associated with significant morbidity and mortality, despite significant advances in conventional treatment. The field of gene therapy has progressed rapidly since the cystic fibrosis transmembrane conductance regulator (CFTR) gene was cloned. In this review we discuss current knowledge on the underlying molecular defect in CF, and the progress in gene transfer studies from the early in vitro work through to clinical trials, including the development of endpoints to assess efficacy. We highlight the problems encountered, and likely future directions of the field.

Adenoviridae↗
PubMedDate not supplied

Tracheal potential difference in the reserpine and isoproterenol rat models of cystic fibrosis.

Basic research into cystic fibrosis (CF) has been hampered by the lack of a suitable animal model. Reserpinized or isoproterenol-treated rats have been proposed as models because they exhibit certain morphological and physiological features characteristic of CF. Recent evidence suggests that abnormal epithelial transport of Na+ [corrected] and Cl- may underlie pathogenesis, defects that may contribute to the markedly more negative transepithelial electrical potential differences (PD) recorded in CF airways compared with controls. To test the models further, we measured tracheal PD in vivo in treated rats (reserpinized - 6.9 mV, SEM 0.7 mV, n = 7; isoproterenol-treated -10.2 mV, SEM 1.5 mV, n = 12) and found it to be no different from that of controls (-8.7 mV, SEM 0.6 mV, n = 25). The animals did, however, demonstrate a reduced gain in body weight as well as increased submaxillary gland weight, which reflected an increased mucus content in the acini. These observations suggest that although the reserpinized or isoproterenol-treated rat may be useful in the study of the pathogenesis of exocrine disturbances in disease, their use as models for the effect of the basic defect of CF in the airways may be limited.

Animals↗
PubMedDate not supplied

Effects of purified Pseudomonas rhamnolipids on bioelectric properties of sheep tracheal epithelium.

The effects of purified rhamnolipids from Pseudomonas aeruginosa on short circuit current in respiratory epithelium have been studied in sheep tracheal epithelium mounted in Ussing chambers under short circuit conditions. In low concentrations (100 microM) mucosal addition of rhamnolipids produces a decrease in short circuit current of 22% and in conductance of 4%. At higher concentrations (> 100 microM), large increases in tissue conductance accompany a greater reduction in short circuit current, suggesting disruption of the intercellular junctions. Serosal addition of rhamnolipids has no effect on ion transport. Pretreatment of the tissues with the sodium channel blocker amiloride (100 microM) or bathing the mucosal surface with sodium-free solution significantly decreased the rhamnolipid-induced fall in short circuit current but did not prevent it completely. Inhibition of chloride transport, sodium-glucose cotransport, and bicarbonate secretion with bumetanide, phloridzin, and acetazolamide, respectively, did not significantly alter the rhamnolipid effect. This suggests that the effect of rhamnolipids on short circuit current is mediated predominantly but not exclusively by an effect on sodium transport. The effects of rhamnolipids on ion transport occur at concentrations within the range occurring in the sputum of patients with cystic fibrosis. The changes in ion transport may explain some of the known effects of rhamnolipid on mucociliary clearance.

Acetazolamide↗
PubMedDate not supplied

Prospects for respiratory gene therapy.

Over the last 5 years a number of articles have been published on gene therapy for a range of diseases. The initial tone of a number of these articles evoked high expectations, particularly from the public. Over the last 2-3 years data from these studies have begun to filter through and, perhaps not surprisingly, initial problems have been encountered, resulting in a recent spate of bad press for gene therapy. This article aims to examine where the prospects for respiratory gene therapy lie in the face of these mixed reactions.

Adenoviruses, Human↗