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Biomedical subjects

N Berend

Publications and source records attributed to N Berend.

18 recordsLinked to original sources

Effects of inhalation of N-formyl-methionyl-leucyl-phenylalanine in the well elderly and in patients with chronic bronchitis.

BACKGROUND: Inhalation of the bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) produces bronchoconstriction in normal subjects. FMLP thus has a putative role as a mediator of bronchoconstriction associated with bacterial bronchial infection. METHODS: The effects of FMLP inhalation were examined in ten subjects with a history of chronic bronchitis and ten age matched control subjects. Each subject inhaled FMLP doses from 0.025 to 0.8 mumol to determine the provocative dose of FMLP causing a 20% fall in FEV1(PD20FMLP). FEV1 was recorded every five minutes after the final FMLP inhalation until it had returned to 95% of baseline FEV1 or 60 minutes had elapsed. The time to return to 95% baseline FEV1 was recorded or extrapolated from the recovery curve as an index of rapidity of recovery. Total and differential white cell counts were performed on each subject at baseline and five and 15 minutes after the final FMLP inhalation. RESULTS: The geometric mean PD20 FMLP in the patients with chronic bronchitis was 0.06 mumol (95% confidence interval 0.015-0.26), which was significantly lower than that in the control subjects (0.21 mumol (0.02-1.9)). PD20 FMLP in the patients with chronic bronchitis but not age matched controls (p = 0.35) was lower than that found previously in young normal subjects (0.35 mumol (0.07-1.8). The return to 95% baseline FEV1 occurred after 86(10) minutes in subjects with chronic bronchitis and in 81(23) minutes in their age matched controls, in both cases being much slower than that seen in young subjects (29(9) minutes). CONCLUSION: Patients with chronic bronchitis may be especially susceptible to formyl peptides elaborated by bacteria during bacterial bronchial infection.

Administration, Inhalation

Haematological effects of inhalation of N-formyl-methionyl-leucyl-phenylalanine in man.

BACKGROUND: N-Formyl-methionyl-leucyl-phenylalanine (FMLP) is a bacterial oligopeptide which stimulates neutrophil chemotaxis, degranulation and superoxide generation. Inhalation of FMLP produces bronchoconstriction in man; in the rabbit this is in part neutrophil dependent. The effects of inhalation of FMLP on peripheral blood leucocytes in normal subjects has been studied. METHODS: This was an open study in non-asthmatic subjects. Change in total peripheral white cell count were studied for 15 minutes after inhalation of 0.4 mumol FMLP in six subjects. Change in total and differential white cell count and spontaneous neutrophil chemiluminescence were then studied five and 30 minutes after inhalation of 0.4 mumol FMLP (n = 7) or diluent (n = 4). Finally, leucocytes from three subjects were labelled ex vivo with technetium-99m labelled sulphur colloid and reinfused. The effect of inhalation of FMLP or diluent on pulmonary neutrophil flux was studied by continuous gamma scanning of a pulmonary window. RESULTS: Leucopenia occurs rapidly after inhalation of FMLP, the nadir of the white cell count (53% of baseline) occurring at four minutes. This was followed by a rebound increase in white cell count evident at 15 minutes (154% of baseline). Five minutes after inhalation of 0.4 mumol FMLP, neutropenia (17% of baseline) and monocytopenia (40% of baseline) were seen followed again by a neutrophilia (213% of baseline at 30 minutes). The eosinophil count was significantly reduced at 30 minutes (24% of baseline). Neutrophil chemiluminescence was elevated (186% of baseline) at the time of the neutropenia. There was no influx of labelled cells to the lung during the period of neutropenia. CONCLUSION: FMLP inhalation activates circulating leucocytes. In vivo production of FMLP in the airway could contribute to bronchial inflammation during bacterial infection.

Administration, Inhalation

Effect of the chest wall and blood volume on pulmonary distensibility.

To determine the reason for increased pulmonary distensibility in excised lungs, we performed deflation pressure-volume (PV) studies in 24 dogs. Exponential analysis of PV data gave K, an index of distensibility. Lung volume was measured by dilution of neon. Compared with measurements obtained in the supine position, with the chest closed, and with esophageal pressure (Pes) to obtain transpulmonary pressure, K was not changed significantly with the chest strapped, with pleural pressure to obtain transpulmonary pressure, or with the chest open. From displacement of PV curves obtained in the supine position and with the chest closed or open, we estimated that Pes was 0.18 kPa greater than average lung surface pressure. An increase in K in the prone and head-up positions was attributed to a traction artifact decreasing Pes. Exsanguination increased K and produced a relative increase in gas volume. These results show that overall pulmonary distensibility is unaffected by an intact chest wall. An increase in K and gas volume after exsanguination probably reflects a decreased pulmonary blood volume, with collapse of capillaries increasing the alveolar volume-to-surface ratio.

Animals

Effects of prolonged inhalation of N-formyl-methionyl-leucyl-phenylalanine in rabbits.

On the basis of its potent proinflammatory and spasmogenic effects, N-formyl-methionyl-leucyl-phenylalanine (FMLP), a bacterial oligopeptide, is a putative mediator of bronchoconstriction and airway inflammation during bacterial bronchial infection. However, after an FMLP dose-response curve in rabbits, tachyphylaxis to a second challenge was seen in some rabbits and airway inflammation was absent. This study was designed to reproduce the more prolonged airway exposure to FMLP that may occur during bacterial infection. Two groups of rabbits received FMLP [5 mg/ml in 66% dimethyl sulfoxide- (DMSO) saline] or DMSO diluent alone by nebulization every 15 min for 2 h. Pulmonary resistance (RL) was measured at 1 and 2 h. Recovery from bronchoconstriction was also assessed by measuring RL every 30 min for 2 h after the final FMLP administration. Sections of trachea and large bronchi were prepared and graded by quadrant from 0 to 3 for inflammation, a total score from 0 to 12 being given for each section. There was a progressive increase in RL in FMLP-treated rabbits, reaching 68 +/- 9% above baseline after 120 min, a significantly greater change than after diluent, 8 +/- 12% (P less than 0.01). RL remained elevated above baseline for 90 min after the final FMLP dose. Inflammation scores were greater after FMLP than DMSO: 9.3 +/- 0.5 vs. 4.3 +/- 0.7 (P less than 0.01) in trachea and 5.2 +/- 0.4 vs. 1.7 +/- 0.5 (P less than 0.01) in lobar bronchi. We conclude that prolonged exposure of airways to FMLP produces a sustained increase in RL and airway inflammation, the cardinal features of infective exacerbations of chronic airflow limitation.

Administration, Inhalation

The influence of food on the bioavailability of new formulations of erythromycin stearate and base.

1. The effect of food on the bioavailability of two new formulations of erythromycin, 1) erythromycin stearate, 500 mg (Erythrocin, 250 mg capsule-shaped tablets) and 2) erythromycin base, 500 mg (Eryc, 250 mg capsules containing enteric-coated pellets) was studied in 16 healthy subjects. 2. The study was a balanced, randomized Latin square design and was conducted on 4 days. The four treatments were erythromycin stearate immediately before (EB) and after EA) breakfast and erythromycin base immediately before (eB) and after (eA) breakfast. 3. The mean +/- s.d. maximal plasma erythromycin concentrations were 2.09 +/- 1.06, 0.37 +/- 0.40, 1.8+ +/- 1.15 and 1.91 +/- 1.57 micrograms/ml and the mean +/- s.d. times at which these occurred were 1.3 +/- 0.7, 2.3 +/- 0.9, 4.4 +/- 1.9 and 4.3 +/- 1.1 h for EB, EA, eB and eA respectively. 4. The mean +/- s.d. areas under the curves (0 to 8 h) were 4.99 +/- 2.41, 1.04 +/- 1.57, 4.93 +/- 2.98 and 4.98 +/- 3.14 for EB, EA, eB and eA respectively. 5. The bioavailability of erythromycin stearate was significantly reduced by the prior administration of food, whereas the absorption of the base was not inhibited by food.

Adult

Combined cholinergic antagonist and beta 2-adrenoceptor agonist bronchodilator therapy by inhalation.

The bronchodilator effects of 40 microgram ipratropium bromide (I) and 400 microgram fenoterol (F) by pressurised aerosol and both drugs in combination were compared with placebo (P) in a double-blind study in eight patients with chronic, partially reversible airways obstruction. The four treatments were (1) IP, (2) PF, (3) IF and (4) PP, with the second aerosol administered two hours after the first. Both drugs produced significant bronchodilatation for five hours, the response being greater and more rapid in onset with fenoterol. Both drugs in combination (IF) produced significant additive bronchodilatation from three to six hours after fenoterol. This additive effect may have been due to the improved lung function caused by ipratropium bromide and does not imply a synergistic effect. There were no side-effects reported. The results suggest that both ipratropium bromide and fenoterol are effective bronchodilating agents in patients with chronic asthma.

Adult

Tracheobronchopathia osteochondroplastica.

The clinical, pathological and physiological features of two patients suffering from tracheobronchopathia osteochondroplastica (TO) are described. Unequivocal evidence of extrapulmonary airways obstruction was not able to be obtained by lung function testing, despite extensive central airway involvement in both patients. TO is a rare condition of which there is only one other clinical report from this country. As the bronchoscopic appearance may closely resemble that of endobronchial neoplasms, TO should be remembered in the differential diagnosis of patients with haemoptysis.

Aged

Relationship between bronchial and arterial diameters in normal human lungs.

In order to find an objective method for measuring narrowing of small airways, eight lungs from four people without lung disease were inflated and fixed at 25 cm of water pressure. Eight to nine blocks were taken at random from each of six parasaggital slices from each lung, sectioned, and stained. The size of the bronchioles (airways without cartilage) in relation to their accompanying arteries was determined. The internal bronchiolar diameter was compared with three different arterial diameters (the internal, external medial, and external adventitial). The ratio of the internal bronchiolar diameter to the external adventitial arterial diameter was constant between lungs (0.62 +/- 0.02) and independent of the method of inflation or the position within the lungs. This ratio may provide a useful index of bronchiolar narrowing in disease.

Adolescent

Correlation between the function and structure of the lung in smokers.

To study the relationship between morphologic changes and alteration of lung function, the excised lobes of 21 smokers and one nonsmoker who required lobectomy for small peripheral tumors were inflated and fixed in formalin, and measurements of bronchiolar narrowing and degree of emphysema were made. All patients had comprehensive pulmonary function tests (including diffusing characteristics, the single-breath N2 test, measurements of elastic recoil, and flow-volume measurements with air and helium) performed before lobectomy. Eight of the lobes excised from the smokers had emphysema of grade 15 or more, the greatest being grade 50. Lobes from 11 patients had evidence of airway narrowing. There were 6 lobes with both emphysema and airway narrowing. Pulmonary function was abnormal in some aspect in all lobes except that from the nonsmoker. Whereas the tests of diffusing capacity, particularly the fractional uptake of CO, correlated with the degree of emphysema, the tests of elastic recoil were not predictive of this early degree of emphysema. The degree of small-airway narrowing correlated with maximal mid-expiratory flow rate and the single-breath N2 test. The maximal flow/static recoil pressure curves were the most sensitive indicators of airway abnormality in the patients with emphysema.

Aged

Plasma and saliva concentrations for a new formulation of erythromycin stearate.

Erythromycin saliva and plasma concentrations were determined in 10 subjects after the first and fourth doses of a new formulation of erythromycin stearate ('Erythrocin'), 500 mg 8-hourly, taken immediately before food. Consistent absorption occurred and the steady state plasma levels compared favourably with the minimal inhibitory concentrations of erythromycin for common respiratory pathogens. There was a significant positive correlation between steady state saliva and plasma levels.

Administration, Oral

Arrest of alveolar multiplication in kyphoscoliosis.

A detailed morphometric study of the lungs of an adult patient with severe kyphoscoliosis of childhood onset is reported. The number of alveoli was less than the normal adult range and corresponded to the predicted values for a 12-month-old infant. This may have been a result of both premature cessation of alveolar multiplication as well as alveolar atrophy. The alveolar size was larger than normal suggesting that after cessation of alveolar multiplication further lung growth occurred by an excessive increase in alveolar size.

Female

Salbutamol by pressure-packed aerosol and by intermittent positive pressure ventilation in chronic obstructive bronchitis.

The forced expiratory volume in one second (FEV1) response to salbutamol administered by pressure-packed aerosol 200 microgram, and intermittent positive pressure ventilation (IPPV), 5 and 10 mg, was determined in 60 patients with chronic bronchitis with airway obstruction. The bronchodilator response to salbutamol by IPPV was greater than by pressure-packed aerosol only in patients with severe airways obstruction and little additional benefit was gained with the 10 mg dose.

Aerosols

Assessment of combined oral theophylline and inhaled beta-adrenoceptor agonist bronchodilator therapy.

1. The bronchodilator effects of 500 microgram rimiterol by pressurized aerosol, 375 mg oral theophylline and both drugs in combination were compared in a randomized, placebo-controlled, double-blind trial in eight patients with chronic, partially reversible airways obstruction. 2. The four treatments were (i) oral theophylline, placebo aerosol (TP); (ii) oral placebo, rimiterol aerosol (PR); (iii) oral theophylline, rimiterol aerosol (TR) and; (iv) oral placebo, placebo aerosol (PP). The aerosol was administered 2 h after the oral treatment. 3. Significant bronchodilatation (% FEV1 change from control) compared to PP occurred with TP from 60 to 480 min and with TR from 60 to 300 min, whereas with PR only for 45 min (P less than 0.05). 4. The mean, peak % FEV1 increases from control were 51.8% at 125 min, 31.7% at 125 min, 26.1% at 210 min and 0.9% at 30 min for TR, PR, TP and PP respectively. 5. At 125 min (5 min after aerosol inhalation) the mean % FEV1 change from control with TR (51.8%) Was significantly greater than with PR (31.7%), TP (22.2%) (P less than 0.05) and PP (-2.4%) (P less than 0.01). 6. The mean, peak plasma theophylline levels were 10.19 microgram/ml at 120 min and 9.98 microgram/ml at 180 min with TR and TP respectively. Theophylline half-life ranged between 4.3 and 12.5 h (mean +/- s.e. mean, 8.0 +/- 0.8 h). 7. Additive bronchodilatation was produced when rimiterol was administered with theophylline at a time when therapeutic plasma theophylline levels were achieved.

Administration, Oral

Characterization of beta-adrenoceptor subtype mediating the metabolic actions of salbutamol.

1. The following four intravenous treatments were administered in a balanced, randomized, Latin square design to four healthy volunteers: (1) saline injection (10 min); salbutamol infusion (0.15 microgram kg-1 min-1 for 60 min) (sS), (2) propranolol injection (0.3 mg kg-1 for 10 min); salbutamol infusion (pS), (3) practolol injection (2 mg kg-1 for 10 min); salbutamol infusion (PS) and (4) saline injection; saline infusion (ss). 2. Heart rate was recorded and venous blood taken for estimation of insulin, glucose and potassium before and after each injection (0 and 12-15 min) and at various times during the infusion (30,45,60 and 75 min). 3. The mean, peak % heart rate changes from baseline, control were +65.8%, +23.0%, -10.9% and -12.1%, the mean, peak % glucose changes, +61.0%, +7.1%, +3.6% and +6.9%, and the mean, peak % insulin changes, +298%, +28%, -28% and -43% during the infusions for sS, PS, ss and pS respectively. 4. The mean serum potassium levels before the injections and at the completion of the infusions were 3.98 and 3.08 4.03 and 3.63, 4.07 and 4.15, and 4.03 and 4.13 meq/l for sS, PS, ss and pS respectively. 5. Propanolol completely abolished the cardiac and metabolic responses of salbutamol. 6. Practolol produced only partial cardiac beta-adrenoceptor blockade, but completely inhibited the metabolic actions of salbutamol.

Adult

The effects of smoking on the lungs.

The literature relating to tobacco smoking has been reviewed and is discussed under a number of headings. The smoking habits of Australians and people of other countries, the constituents of tobacco smoke and the different types of tobacco are discussed. The effects of tobacco smoke on lung defences and and function are outlined and the evidence relating cigarette smoking to lung cancer in Australia, the UK and the USA is reviewed. The relationship between cigarette smoking and diseases which chronic air flow obstruction is outlined. Differences in smoking-related diseases in males and females and the effects of stopping smoking are included in the discussion.

Adolescent