Search PubMed⌕ Search

Biomedical subjects

D M Geddes

Publications and source records attributed to D M Geddes.

At least 145 records · Page 8Linked to original sources
PubMed1990

Effect of inhaled furosemide on metabisulfite- and methacholine-induced bronchoconstriction and nasal potential difference in asthmatic subjects.

To evaluate the hypothesis that furosemide inhibits indirect bronchoconstrictor challenges by altering airway epithelial ion transport, we studied its effects on indirect bronchoconstriction induced by inhaled metabisulfite (MBS) and nasal potential difference (PD) in seven subjects with mild asthma. Its effect on direct bronchoconstriction by the inhaled muscarinic agonist methacholine (MC) was studied in six of these subjects. Each subject inhaled furosemide, 30 mg, in a randomized, double-blind, placebo-controlled fashion immediately before challenge with MBS (0.3 to 160 mg/ml in increasing doubling concentrations) and, in another study, MC (0.125 to 32 mg/ml) aerosols from a nebulizer attached to a dosimeter. PC20MBS and PC20MC, the concentration of each agent needed to lower FEV1 by 20%, were calculated by linear interpolation of the log dose-response curves. Furosemide had no effect on resting lung function, but it caused a significant threefold reduction in sensitivity to MBS (PC20MBS: GM +/- GSEM, 15.1 +/- 1.6 mg/ml after placebo and 40.7 +/- 1.7 mg/ml after furosemide; p less than 0.001) with a protective index of 64.8 +/- 10.7%. Furosemide caused no change in sensitivity to MC (PC20 MC:GM +/- GSEM, 2.37 +/- 1.61 mg/ml after placebo and 2.19 +/- 1.751 mg/ml after furosemide; NS). In a third study, furosemide, 30 mg, and placebo were inhaled through the nose in a randomized double-blind fashion immediately prior to inhalation of a PC20 concentration of MBS through the nose. Nasal PD was measured before and after placebo or furosemide, and again after MBS inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1990

Nasal potential difference: a clinical diagnostic test for cystic fibrosis.

Patients with cystic fibrosis (CF) demonstrate a markedly more negative potential difference (PD) across respiratory epithelia than normal or "diseased" controls. A technique is described for the measurement of nasal PD in both children and adults. 145 non-CF subjects showed a mean PD of -19.0 mV (range -2 to -36) in comparison to 60 patients with cystic fibrosis with mean of -46.0 mV (range -32 to -77). Amongst the latter group those with more severe disease had a more negative PD. Measurement of nasal PD is easily learnt and rapidly performed and may provide an additional means of diagnosis for CF.

Adolescent↗
PubMed1989

Intensive chemotherapy with autologous bone marrow transplantation for small-cell lung cancer.

Since 1980, 75 patients with small-cell lung cancer (SCLC) have been entered into four consecutive studies of high-dose chemotherapy using autologous bone marrow transplantation (ABMT) to assist haematological recovery. In the first study, 25 patients were treated with cyclophosphamide (160-200 mg/kg) as the sole chemotherapy; in the second (26 patients), the cycle of high-dose cyclophosphamide (with or without 800-1,200 mg/m2 etoposide) was repeated as induction treatment. In the first study, response was high [14 complete responses (CR), 7 partial responses (PR)] but was not increased by repeating the cycle (15 CR, 8 PR), and survival was slightly worse in the second trial. In the third study, 15 patients were treated with doxorubicin, vincristine and etoposide for two cycles and then with 200 mg/kg cyclophosphamide. Although high-dose cyclophosphamide increased the complete response rate, the additional responses were short-lived. In the final study, an attempt was made to increase the initial CR rate by combination chemotherapy using carboplatin (400-600 mg/m2), etoposide (120 mg/m2 x 4) and either high-dose cyclophosphamide (40 mg/kg x 4) or melphalan (140 mg/m2). Although all nine patients responded, none underwent a CR. The long-term survival (up to 7 years) does not appear to be different from that in comparably selected cases treated with conventional chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

High frequency oscillations and mucociliary transport.

Mucociliary transport is influenced by high frequency oscillation of air within the lungs. While some studies suggest that high frequency ventilation may be detrimental, with appropriate techniques, there is no doubt that this has potential as a means of improving the clearance of secretions from the lung.

Airway Resistance↗
PubMed1989

Duration of chemotherapy in small cell lung cancer: a Cancer Research Campaign trial.

A total of 610 patients with small cell lung cancer were entered into a randomised trial designed to assess the effect of duration of initial chemotherapy on survival. Patients were randomised to receive either four or eight courses of cytotoxic chemotherapy with cyclophosphamide, vincristine and etoposide and also randomised to receive, on disease progression, either second line chemotherapy (methotrexate and doxorubicin) or symptomatic treatment only. In the whole study 196 (32.1%) had limited disease and 414 (67.9%) extensive disease. During initial chemotherapy the response rate (complete and partial responses) after four courses of treatment was 61% with no significant increase in patients receiving eight courses (63%). In those randomised to receive relapse chemotherapy the response rate was improved slightly for those who had originally received four courses of chemotherapy (25.6%) over those receiving eight (18.7%). The overall results show that of the four possible treatment randomizations, four courses of chemotherapy alone is inferior in terms of overall survival (30 weeks median survival) to the other three treatment options (39 weeks median survival, P less than 0.01). In patients responding to initial chemotherapy the disadvantage of four courses of chemotherapy alone was apparent (median survival of 40 weeks versus 49 weeks, P = 0.003) but not if drug treatment was given on relapse. The study shows that limiting treatment to four courses of chemotherapy alone is associated with inferior survival, but this is not the case if chemotherapy is given at relapse.

Adult↗
PubMed1989

Spinal cord compression in small cell lung cancer: a retrospective study of 610 patients.

The records of 610 consecutive patients with small cell lung cancer, treated on a common protocol in a multicentre trial, were reviewed and 24 (4%) cases of spinal cord compression identified. Five hundred patients had isotope bone scans performed at presentation, and in 131 (26%) there was abnormal isotope uptake in the spinal column; only 7% of these patients developed spinal cord compression. However, of the 24 patients who presented with back pain and had a positive bone scan affecting the spine, 36% developed cord compression. Cerebral metastases occurred at some stage in 19.5% of all patients and in 45% of patients with cord compression. The combination of cerebral metastases and a positive bone scan gave a 25% chance of developing spinal cord compression. There were two distinct forms of clinical presentation. Six patients (group A) presented with cord compression: All had back pain and positive bone scans, five out of six had sphincter disturbance, and median survival from cord compression was 30 weeks. Eighteen patients (group B) developed cord compression while on treatment: 28% had positive initial bone scans, 44% back pain and 61% sphincter disturbance, and median survival from cord compression was 4 weeks. Spinal cord compression is an important cause of morbidity and mortality in small cell lung cancer. We suggest that it may be possible to select patients who should receive radiotherapy to the spine to try to prevent the development of this complication.

Adult↗
PubMed1989

Patients at risk of chemotherapy-associated toxicity in small cell lung cancer.

During a clinical trial of duration of chemotherapy in small cell lung cancer (SCLC), 71 of 610 patients (11.6%) died in the first 3 weeks. Chemotherapy consisted of cyclophosphamide 1 g m-2 i.v. day 1, etoposide 100 mg t.d.s. orally days 1-3, vincristine 2 mg i.v. day 1. The time of death was found to be nonrandomly distributed within the first chemotherapy cycle, with a peak incidence between days 7 and 12 after chemotherapy. Patients were matched with controls who were the next cases entered into the study who did not die in the first 3 weeks. Patients dying early were more likely to have clinical hepatomegaly (P less than 0.0001), and ECOG score greater than or equal to 1 (P less than 0.00001). As a group these patients also had a higher alkaline phosphatase (P less than 0.0002), an elevated blood urea (P less than 0.00001) and a lower serum albumin (P less than 0.0001) than controls. It is probable that infection contributes to the death of these already ill patients at a time when the blood count is low. Early deaths have been noted in two other large trials using regimens including etoposide. Prophylactic antibiotics or dosage modification may prevent the early death of these high risk patients.

Adult↗
PubMed1989

Cystic fibrosis--from lung damage to symptoms.

Respiratory symptoms in cystic fibrosis are both local and systemic. The local symptoms include cough, sputum, wheezing, haemoptysis and breathlessness, while systemic symptoms of malaise and fever occur with pulmonary infection. There are also interactions between respiratory and gastrointestinal systems in producing symptoms of malaise and weakness and these also contribute to the secondary psychological and social problems that a number of patients with cystic fibrosis experience. These local respiratory symptoms can be attributed in part to lung damage, but are also a manifestation of the CF defect itself. Similarly, lung damage, allergy, haemodynamic and nutritional changes all contribute to the symptom of breathlessness. Further improvement in symptoms in the future will come not only from limiting the lung damage but also from therapy aimed at reversing the CF defect itself.

Cystic Fibrosis↗
PubMed1989

Respiratory aspects of Shwachman's syndrome in adults.

Shwachman's Syndrome is a rare disorder which causes considerable morbidity in childhood and can be confused with cystic fibrosis. Six patients (4 males; mean age 27 yrs) are described in order to illustrate the clinical picture of the syndrome in adults. Recognized features persisting in later life include pancreatic insufficiency and bone marrow dysfunction (all patients), short stature (5/6), advanced dental caries (4/6), and impaired glucose tolerance (2/6). Chest radiograph was normal in all patients whilst lung function tests showed mild restriction in three and obstruction in two. All patients were cyclically neutropenic (nadir count 2.1 x 10(9).l-1). Four of the six patients were thrombocytopenic and three had persistent immunoglobulin deficiencies. Neutrophil chemotaxis was abnormal in four patients and the nitro blue tetrazolium test was abnormal in a fifth. Two patients suffered from recurrent respiratory infections, one of whom died from bone marrow aplasia. Although Shwachman's Syndrome may be less troublesome in adults than in children, many of the abnormalities persist into adult life and may continue to cause diagnostic difficulty.

Adult↗
PubMed1988

Aerosol deposition in the human lung: effect of high-frequency oscillation on the deposition characteristics of an inhaled nebulized aerosol.

1. Oral high-frequency oscillation (OHFO) may have important effects on aerosol deposition in the lungs. In order to investigate these, a technique was devised to measure regional deposition rates of a nebulized radiolabelled aerosol in the lungs during normal tidal breathing. 2. The effect of three frequencies of OHFO on pulmonary aerosol deposition rate (PADR) in four normal subjects and five patients with chronic airways obstruction (CAO) were assessed using the technique. 3. In separate experiments employing three normal subjects, the effect of OHFO was studied on the deposition rate of aerosol on the oropharynx and delivery apparatus, and on the amount and characteristics of aerosol inhaled by the subjects. 4. Total PADR was significantly reduced by OHFO at 8 Hz and 16 Hz in the normal subjects, and by all three frequencies of OHFO in the CAO patients. In the normal subjects, the regional distribution of aerosol deposition was unchanged, but in the CAO patients a larger proportion of total aerosol deposition occurred in peripheral lung. 5. OHFO reduced the oropharyngeal aerosol deposition rate, increased the loss of aerosol to the atmosphere before inhalation, and increased the deposition of aerosol on the delivery apparatus. The end result was a reduction in the amount of aerosol inhaled, and in the particle sizes measured at the mouthpiece. 6. We conclude that OHFO reduces the amount of aerosol inhaled, but may improve peripheral deposition of inhaled aerosol in patients with CAO. This effect may be of value in the clinical administration of nebulized drugs.

Aerosols↗