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Biomedical subjects

D M Geddes

Publications and source records attributed to D M Geddes.

At least 199 records · Page 11Linked to original sources
PubMed1983

High-dose cyclophosphamide with autologous marrow transplantation for small cell carcinoma of the bronchus.

Twenty-five patients with previously untreated small cell carcinoma of the bronchus have been treated with cyclophosphamide 160-200 mg/kg and subsequent radiotherapy to the primary site. Eighty-four percent of patients responded to the single cycle of chemotherapy, with 56% attaining a complete response. Median duration of remission was 43 weeks and median survival 69 weeks. 2-Mercaptoethane sulphonate was given to prevent urothelial toxicity. Autologous bone marrow transplantation was used to mitigate bone marrow depression but sequential delay in reinfusing cryopreserved bone marrow did not alter the period of cytopenia. Other toxicities were mild. The procedure proved safe and manageable. High-dose chemotherapy may prove to be useful in the initial management of this tumour.

Adult↗
PubMed1983

Treatment of obstruction of the superior vena cava by combination chemotherapy with and without irradiation in small-cell carcinoma of the bronchus.

In a randomised prospective trial of chemotherapy with and without radiotherapy in small-cell carcinoma of the bronchus, 37 of 366 patients presented with obstruction of the superior vena cava at the time of diagnosis. In the study all patients received four cycles of combination chemotherapy over a period of 12 weeks and, provided there was not progressive disease, then received either radiotherapy to the mediastinum and primary tumour followed by eight further courses of chemotherapy or eight cycles of chemotherapy alone. Of the 37 patients presenting with superior vena caval obstruction, nine had relapsed and treatment was stopped during or after the initial four cycles of chemotherapy. Of the remainder, 15 patients received radiotherapy plus chemotherapy and 13 chemotherapy alone. After four cycles of chemotherapy (12 weeks) 21 of the 37 patients had initial complete relief of symptoms secondary to superior vena caval obstruction, 10 had substantial but partial relief, and six had no relief. Twelve patients developed recurrence of superior vena caval obstruction, of whom six had received radiotherapy and four chemotherapy alone; two relapsed in the initial 12 weeks of the study. The median survival of the patients with superior vena caval obstruction allocated at diagnosis to either treatment arm was identical. The survival of patients with obstruction was similar to that of other patients in the main study. Chemotherapy is an effective treatment for superior vena caval obstruction and there appears to be no additional advantage in giving radiotherapy after 12 weeks of cyclical chemotherapy.

Antineoplastic Agents↗
PubMed1983

Effect of beta-adrenergic blockade on hyperventilation and exercise tolerance in emphysema.

Ventilation, heart rate, and arterial blood gas tensions were measured at rest and during incremental exercise in 10 patients with emphysema after intravenous placebo or 7 mg metoprolol. Metoprolol reduced heart rate by 14% (P less than 0.001) and ventilation by 11% (P less than 0.01), but there was no significant difference in arterial O2 or CO2 tension (Pao2 and PaCO2, respectively). Metoprolol increased the time to exhaustion on a cycle ergometer (P less than 0.05) but did not improve the 12-min walking distance. A double-blind randomized crossover comparison of 4 wk treatment with atenolol (100 mg/day), metoprolol (100 mg/day), or matched placebo was performed in 12 patients with emphysema. Both beta-adrenoceptor antagonists reduced resting heart rate by 33% (P less than 0.001) and resting minute ventilation by 11% (P less than 0.025). There was no change in resting or exercise Pao2 or Paco2. During steady-state exercise on a cycle ergometer, atenolol and metoprolol reduced ventilation by 14 and 4%, respectively. This was accompanied by 11 and 5% reductions in O2 consumption (P less than 0.05) and 13 and 6% falls in CO2 production (P less than 0.05). There were no significant changes in tests of exercise tolerance, but forced expiratory volume in 1 s and forced vital capacity were reduced during beta 1-adrenergic blockade. beta 1-Blocking drugs reduce hyperventilation in emphysema by reducing pulmonary gas exchange without a change in arterial blood gas tensions. Increased airflow obstruction prevents this reduction being of therapeutic value.

Administration, Oral↗
PubMed1983

Breathlessness and exercise tolerance in chronic airflow obstruction: 2-hourly versus 4-hourly salbutamol by inhalation.

Breathlessness, exercise tolerance, and spirometry were measured in 12 patients whose major symptom was breathlessness, secondary to severe chronic airflow limitation, during a double-blind crossover comparison of inhaled salbutamol in two dosages (200 micrograms 4-hourly and 200 micrograms 2-hourly) with placebo. Daily visual analogue scores of breathlessness, exercise tolerance and spirometry were all significantly improved with salbutamol in both dosages compared to placebo. The 2-hourly regimen was superior to the 4-hourly regimen only in terms of exercise tolerance. Walking distance had deteriorated significantly 2 hours after salbutamol on the 4-hourly regimen and was usefully increased by an extra dose of salbutamol on the 2-hourly regimen at the equivalent time, without side-effects. Salbutamol provided considerable symptomatic relief in addition to spirometric improvement in patients with chronic airflow limitation.

Aged↗
PubMed1983

Inhibition of exercise-induced asthma by an orally absorbed mast cell stabilizer (M & B 22,948).

M&B 22,948 (2-o-propoxyphenyl-8-azapurin-6-one) is an orally absorbed mast cell stabilizer which is 30 times as potent as disodium cromoglycate in laboratory and animal studies. In a double-blind placebo-controlled cross-over trial we studied the protection afforded by a single oral dose of 10 mg of M&B 22,948 against asthma induced by histamine and exercise, each in 12 patients. Compared with placebo the drug had no significant effect on the response to inhaled histamine but significantly inhibited the fall in FEV1 induced by exercise on treadmill (P less than 0.005). The exercise-induced fall in FEV1 was less following M&B 22,948 than placebo in all patients and the fall was inhibited by more than 50% in five (42%) of 12 patients. The degree of inhibition was significantly correlated with the plasma drug concentration (r = 0.65, P less than 0.025). M&B 22,948 merits evaluation in the treatment of asthma.

Adolescent↗
PubMed1983

Comparison of vincristine and vindesine in the treatment of inoperable non-small cell bronchial carcinoma.

Sixty-three patients with inoperable symptomatic non-small cell carcinoma of the bronchus were randomly allocated to receive either vincristine (1.4 mg/m2) or vindesine (3 mg/m2). These drugs were given weekly for four doses, then every 2 weeks for two further doses, and then continued monthly if there had been a response. Only five partial responses (greater than 50% reduction) were obtained with vindesine and none with vincristine. Disabling toxic effects occurred in 13 patients. This was more common with vindesine, but this group also received more prolonged therapy. Vindesine has modest activity against non-small cell carcinoma of the bronchus and may be more effective than vincristine, with similar toxicity.

Adult↗
PubMed1982

Epipodophyllotoxin (VP16-213) in small cell carcinoma of the Bronchus resistant to initial combination chemotherapy.

Thirty-eight patients with small cell carcinoma of the bronchus resistant to initial chemotherapy with cyclophosphamide methotrexate and CCNU, were treated with VP16-213 alone in a dose of 120 mg/m2 i.v. on days 1, 3, and 5 every 3 weeks. Twelve patients died before three courses of treatment. In 26 patients who received three or more courses only one, transient partial response occurred. One or more components of the initial chemotherapy seems to confer resistance to the action of VP16-213 in this disease.

Bronchial Neoplasms↗
PubMed1982

High-dose cyclophosphamide with autologous marrow transplantation as initial treatment of small cell carcinoma of the bronchus.

Sixteen patients with untreated small cell carcinoma of the bronchus received cyclophosphamide in a total dose of 160-200 mg/kg. Autologous marrow transplantation was used to minimise the period of hypoplasia and 2-mercaptoethane sulphonate to prevent urothelial toxicity. The procedure was well tolerated, with predictable and manageable toxicity. Complete radiological and bronchoscopic response was achieved in seven patients and partial response in a further seven. High-dose cyclophosphamide may be a useful initial treatment for this disease.

Adult↗
PubMed1982

The selectivity of the beta-adrenoceptor for ventilation in man.

1 Minute ventilation, alveolar PCO2, CO2 production and heart rate were measured in eight normal subjects before and during infusions of noradrenaline 0.2, 1.0 and 5.0 micrograms min-1 and isoprenaline 0.04, 0.2 and 1.0 microgram min-1. 2 These measurements were repeated after propranolol 3.5 mg, atenolol 8 mg or metoprolol 7 mg by intravenous injection. 3 Noradrenaline 5.0 micrograms min-1 and isoprenaline 1.0 microgram min-1 significantly increased ventilation and CO2 production and decreased alveolar PCO2. These changes were attenuated by propranolol, atenolol and metoprolol. There was no significant difference between the blocking effects of the three beta-adrenoceptor blockers for these three variables but propranolol was more effective than atenolol or metoprolol in blocking isoprenaline induced tachycardia (P less than 0.001). 4 The hyperventilatory response to catecholamines is predominantly a beta1-effect.

Adrenergic beta-Antagonists↗
PubMed1982

Carbimazole and exercise tolerance in chronic airflow obstruction.

Ten patients with severe dyspnoea and chronic airflow obstruction entered a randomised double-blind crossover trial comparing the effect of carbimazole 80 mg daily for two months with that of placebo. Assessment of thyroid function, lung function, and exercise tolerance was performed monthly. The mean free thyroxine index after two months of carbimazole was significantly lower at 64.1 (+/- 10.5, SEM) than the 89.1 (+/- 3.8) while on placebo. Serum tri-iodothyronine was reduced and thyroid stimulating hormone raised while on the active drug. There was no significant difference in the 12-minute walking distance (TMD), the rating of perceived exertion during the TMD, the oxygen cost score, the dyspnoea grade, the resting arterialised capillary blood gas tensions or the resting minute ventilation. During a progressive exercise test to exhaustion on a cycle ergometer, there was no significant difference in the minute ventilation, heart rate, blood gas tensions at exhaustion, or the total work done. There were no symptoms or signs of hypothyroidism. Lung function (FEV1, FVC, TLC, KCO) was unchanged. Thus a 28% reduction in the free thyroxine index produced no symptomatic or objective benefit in exercise tolerance in patients with severe airflow obstruction. These results provide no support for the use of carbimazole in chronic airflow obstruction.

Carbimazole↗
PubMed1982

Bronchoscopic and percutaneous aspiration biopsy in the diagnosis of bronchial carcinoma cell type.

The cell type of bronchial carcinoma predicted from the results of bronchial biopsy at fibreoptic or rigid bronchoscopy or of percutaneous aspiration lung biopsy was compared with the type determined by histological examination of specimens obtained by thoracotomy, biopsy of an extrapulmonary metastasis, or necropsy in 180 cases. The rates of agreement with the final diagnosis were 95.7% for bronchial biopsy through the fibreoptic bronchoscope and 86.5% through the rigid bronchoscope. For percutaneous biopsy, which was usually carried out on tumours inaccessible to the bronchoscope, the rate of agreement was 61%, significantly lower than by the other methods (p less than 0.001). The diagnosis of oat-cell carcinoma by any technique was very reliable. Bronchial biopsy was more reliable than was percutaneous biopsy in diagnosing squamous-cell carcinoma. With any technique the commonest error was the incorrect diagnosis of squamous-cell carcinoma or adenocarcinoma as large-cell undifferentiated carcinoma.

Adenocarcinoma↗
PubMed1982

Fibreoptic bronchoscopy: effect of multiple bronchial biopsies on diagnostic yield in bronchial carcinoma.

The findings in bronchial biopsy specimens obtained at fibreoptic bronchoscopy in 271 patients with bronchial carcinoma were reviewed. Fifty-nine per cent of 703 specimens taken from the site of bronchoscopically visible tumours in 215 patients provided evidence of carcinoma. Unequivocal histological evidence of carcinoma was obtained in 78.6% of the 215 patients with visible tumours. When only one biopsy specimen was taken evidence of carcinoma was obtained in 65.2% of cases. At least five biopsy specimens were required to provide a greater than 90% probability of obtaining at least one positive sample. The anatomical site of the tumour had no significant effect on the proportion of biopsy specimens that were positive or the frequency of obtaining at least one positive sample. When extrinsic bronchial compression was the only visible abnormality evidence of carcinoma was obtained by bronchial biopsy in 26.8% of 56 cases.

Adenocarcinoma↗
PubMed1982

Propranolol uptake by dog lung: effect of pulmonary artery occlusion and shock lung.

First-pass lung uptake of propranolol in catheterized ambulant dogs was measured by comparison the difference between the ratios of [14C]propranolol to indocyanine green (ICG) before and after a single passage through the pulmonary circulation. Uptake was 56 +/- 5, 53 +/- 8, and 61 +/- 10% (mean +/- SD) when 0.02, 0.2, and 2.0 mg of propranolol were injected, respectively. There was a negative though unimportant correlation between percent uptake and cardiac output. Analysis of paired propranolol and ICG outflow curves confirmed the lack of saturation with increasing dose and suggested the involvement of simple diffusion. In four dogs uptake fell from 4.76 +/- 6.8 to 40.4 +/- 8.2% (0.05 greater than P greater than 0.025) during partial occlusion of the pulmonary circulation by a Swan-Ganz catheter balloon and rose again to 51.2 +/- 6.4% after relief of the occlusion. Propranolol uptake, measured serially in five dogs with indwelling catheters, was initially 55% but fell linearly to 30% over 2 wk (r = -0.59, P less than 0.001), and necropsy showed pathological features of shock lung. A similar study performed on three dogs within 4 days of catheterization showed no change in uptake of the drug. Propranolol uptake appears to reflect both quantitative and qualitative changes in the pulmonary endothelium. This method may therefore be valuable in studying the pulmonary endothelium in health and disease.

Animals↗
PubMed1982

Impaired lung uptake of propranolol in human pulmonary emphysema.

First-pass lung uptake of propranolol was studied in 10 patients with normal lungs, 8 patients with severe pulmonary emphysema, and 1 patient with primary pulmonary hypertension. Propranolol uptake was measured by comparing the ratio of [14C]propranolol (0.5 mg) to indocyanine green (5 mg) injected into the right atrium with the ratio of their concentrations in arterial blood collected over the duration of the first-pass dye outflow curve. Mean uptake was 69 +/- 4% (n = 18) in patients with normal lungs; 55 +/- 7% (n = 13) in patients with emphysema (p less than 0.001), and 51% in the patient with primary pulmonary hypertension. Cardiac index in the normal group (2.78 +/- 0.48 L/min/M2, n = 16) was not significantly different from the group with emphysema (2.90 +/- 0.48, n = 12). There was no correlation between lung uptake and conventional lung function indexes in patients with emphysema. We conclude that propranolol uptake is reduced when the pulmonary vascular bed is damaged. This may have pharmacologic consequences, and it is possible that other pharmacokinetic functions of the lung may similarly be impaired in pulmonary disease. The method is relatively simple, and may be suitable for assessing pulmonary endothelial function in patients with lung disease.

Adult↗
PubMed1982

Tumor size, response rate, and prognosis in small cell carcinoma of the bronchus treated by combination chemotherapy.

Ninety-eight patients with small cell carcinoma of the bronchus (SCCB) were treated with a combination of cyclophosphamide, methotrexate with calcium leucovorin rescue, and lomustine (CCNU). VP-16-213 was given on relapse. Response rate and survival were analyzed according to extent of tumor, presence of the syndrome of inappropriate antidiuretic hormone production (SIADH), and, in 38 patients, size of intrathoracic tumor as measured by computerized tomographic (CT) scanning. The median survival of the entire group was 34.6 weeks. In patients with limited disease the median survival was 46 weeks compared to 29 weeks for those with extensive disease. This difference in survival between patients with limited and extensive disease was most marked in those showing a partial response (median survival, 45.9 and 28 weeks, respectively). Patients with ectopic antidiuretic hormone production had a poor prognosis even if they had achieved a complete response. Only one partial response to VP-16-213 occurred. There was a strong correlation between initial intrathoracic tumor size as assessed by total cross-sectional area on CT scan and response and survival. When the total area exceeded 30 cm2 there were no complete responders, but there were complete responses in eight of 21 patients when the area was less than 30 cm2. The relationship between intrathoracic tumor size and response rate was present when analyzed according to disease extent, age, sex, and performance status. A clear relationship between total tumor area and survival was also found. When SCCB is treated with chemotherapy alone, the prognosis is better for those patients who present with limited disease, without SIADH, and with small intrathoracic tumor. In this group it is possible that further intensification of therapy may result in prolonged survival.

Adult↗