Biomedical subjects
Publications and source records attributed to W T Ulmer.
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This investigation compared the efficacy of oral formulations of amoxycillin/clavulanate and ciprofloxacin in acute exacerbations of chronic bronchitis. Forty patients were randomized to receive either Augmentin (1,000 mg amoxycillin +250 mg clavulanate) tds or ciprofloxacin (500 mg) bd. During and before therapy sputum samples were taken for bacteriology, sputum volume measurement and histamine determination. Lung function was also monitored. From sputum, 143 bacterial isolates and 15 yeast strains were obtained before therapy. During therapy with amoxycillin/clavulanate the incidence of Gram-positive isolates decreased significantly whereas ciprofloxacin left their frequency unchanged. On the other hand, ciprofloxacin more effectively diminished the incidence of Gram-negative isolates. Yeasts were grown from the sputum of several patients before and during therapy. Their number did not increase during amoxycillin/clavulanate therapy while it increased under ciprofloxacin. The groups showed no significant differences with regard to sputum production, histamine concentration or lung function. The majority of patients (28/40) acknowledged improvement of their symptoms. There was no significant difference between the groups. On the basis of these results both amoxycillin/clavulanate and ciprofloxacin appear of similar value for treatment of patients with exacerbations of chronic bronchitis.
The static compliance was determined in 55 subjects with healthy lungs. Average values are within 2.696 liters/kPa (age between 20 and 30 years) and 1.794 liters/kPa (age between 71 and 80 years). Static compliance was shown to be exclusively related to age (p less than 0.001). Broca index, sex, cigarette smoking and intrathoracic gas volume did not influence static compliance. The relation can best be described by a logarithmic regression equation.
Clinical studies have been carried out world-wide on cefetamet pivoxil, a new orally active cephalosporin. This paper reports on the first 1000 patients treated with the antibiotic; another 505 patients received standard antibiotics, mainly cefadroxil and cefaclor, for comparison. The results show that single doses of 1500 and 1200 mg cefetamet pivoxil were fully effective in gonorrhoea. Comparative trials in uncomplicated urinary tract infection indicate a significant superiority of a single dose of 2 g cefetamet pivoxil (n = 158; 90.0% cure) versus 2 g cefadrox (n = 162; 77.0% cure). In complicated urinary tract infections, a comparable outcome was achieved with a single daily dose of 2 g cefetamet pivoxil for 10 days (n = 99; 90% cure) and 1 g cefadroxil twice daily for 10 days (n = 98; 76.5% cure). The clinical response rate in acute exacerbation of chronic bronchitis was 89.4% in the group receiving cefetamet pivoxil (136 patients) and 83% in the cefaclor-treated group (n = 122). Treatment with 1000 or 2000 mg cefetamet pivoxil achieved a (bacteriological) success rate of 96% compared to 95% with cefaclor in acute ear, nose and throat-infections (n = 91). Overall, based on 894 isolated pathogens prior to therapy, the bacteriological response rate was 90% and it would appear that in vivo the spectrum of this cephalosporin covers a wide range of Gram-negative and Gram-positive pathogens, including urinary pathogens, but excluding Enterococci and Pseudomonas. Cefetamet pivoxil proved to be well tolerated. Mild to moderate adverse events were reported in 7.1% of patients but only 2 of the 1000 patients treated with cefetamet pivoxil were withdrawn because of diarrhoea, which subsided rapidly. There were no clinically relevant deviations in laboratory parameters.
In a pilot study 8 patients with allergic obstructive airway disease were treated with the new compound picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarine++ + dihydrochloride) 2 x 2 mg daily orally during a period of 8 days additionally to a usual therapy of bronchodilators and corticoids in a steady state. It was demonstrated that the compound inhibited the allergen induced histamine liberation of patients basophils significantly. Compared with a collective of patients without an additional picumast dihydrochloride treatment the effect of the substance was shown more clearly. From reasons of these experimental data picumast dihydrochloride may be of a considerable value as a prophylactic agent in allergic bronchial asthma when given orally.
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Respiratory responses during allergen-induced airway obstruction and external airway stenosis were investigated in anaesthetised sheep. The results were compared to those obtained from healthy subjects during external airway stenosis. Allergen-induced increase in airway resistance results in an increased respiratory frequency, mainly due to a shortening of expiration (TE) and only partially due to a shortening of inspiration (TI). Tidal volume is diminished while respiratory changes in oesophageal pressure (delta Poes) are increased. Both results in an increase of dynamic elastance (Edyn) representing airway resistance. Based on the increase in the slope and amplitude of inspiratory pressure (delta Poes/TI), the mean inspiratory airflow (VT/TI) remains almost unchanged. In spite of an increased ventilation PaO2 decreases, whereas PaCO2 increases only slightly. External airway stenosis, however, results in a decrease of respiratory frequency, mainly depending on a prolongation of inspiration. Changes in Poes and VT are similar to those of allergen-induced airway obstruction. delta Poes/TI, however, increases less than during allergen application and results in a decrease of mean inspiratory airflow, tidal volume and ventilation. Respiratory responses of healthy subjects during external airway stenosis were similar to those described in experimental animals. The results of our investigation show a different pattern in the control of breathing during bronchial and external stenosis-induced airway obstruction and thus indicate different vagal reflex mechanisms.
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140 bakers with occupation-related asthma symptoms and/or rhinoconjunctivitis were tested for specific IgE antibodies against various enzyme-containing baking components. 5-24% of subjects were sensitive to several carbohydrate-splitting enzymes obtained from mould fungi (amyloglucosidase, hemicellulase and alpha-amylase), as well as/or against soya flour. But allergies against the proteolytic enzymes papain and B. subtilis protease were rare (about 1%). These results indicate that various baking components, especially mould enzymes, play a not insignificant role in the causation of baker's asthma.
In a six-month multicenter feasibility and safety study, 20 patients, who all had a congenital deficiency of alpha-1-protease inhibitor (A1PI) of the PiZ phenotype accompanied by a chronic obstructive lung disease, were treated with human-plasma-derived A1PI. A weekly dose of 60 mg/kg, administered intravenously, was shown to be sufficient to maintain patient serum levels above the threshold limit of 35 percent, the serum level of healthy persons of the MZ phenotype. This is supposed to be the minimal effective level for protection against the elastolytic attack of the lung and, therefore, satisfies one of the most important criteria of feasibility of long-term replacement therapy. The global concentration in serum or bronchiolar lavage fluid A1PI including active and inactivated A1PI was measured immunologically by rate nephelometry and radial immunodiffusion. The functional activity of A1PI, expressed as free inhibitor activity against trypsin and leukocyte elastase, confirmed that the infused A1PI remained mostly in its active form in the circulation. Reported adverse reactions were moderate and did not require alteration to the schedule of the infusions and/or the dose and rate of administration. Antibodies to A1PI as measured by the Ouchterlony method did not develop. Laboratory and physical signs of possible hepatitis virus contamination were not observed. The long-term replacement therapy, therefore, appears to be safe.
Using the nowadays available therapeutic means for patients with chronic obstructive lung diseases it is, even with severe forms of emphysema, possible to obtain excellent results. This is mainly due to elimination of increased flow resistance in the airways. These great advances should not conceal that the common life expectancy is not yet obtained in this group of patients. In spite of the fact that an acceptable quality of life can be provided during long-term therapy these patients are ill. It is hoped that with the available knowledge on prevention, early treatment and new therapeutic approaches progress to chronic disease may be avoided.
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In a multi-centre study 20 patients with severe congenital alpha-1-Pi deficiency and progressive pulmonary emphysema received infusions of alpha-1-Pi concentrate from human plasma once weekly for six months, at an initial dosage of 60 mg/kg body-weight, in some instances slightly increased to achieve a minimum serum level above 70 mg/100 ml. The immunologically measured serum level of alpha-1-Pi rose 30 min after start of the infusion by a mean of 130% of normal, at an initial level of 13%. An exponential fall followed this rise. The lowest level occurred at the end of the first week, immediately before the next infusion, to 35% of normal, a serum level which is assumed still to provide an effective protection against elastases in the lung. There was also a definite increase of free inhibitors against both trypsin and leucocyte-elastase in serum of all patients, with a minimal level which for both was many times that of the initial value. There were no side-effects in more than 500 infusions and no dose reduction was necessary. During the entire course there were no significant changes in haematological, coagulation and biochemical test results, and lung function means remained constant. No antibodies against alpha-1-Pi were demonstrated, nor transmission of hepatitis B.
Previous investigations have demonstrated high histamine concentrations in the sputum of patients with chronic obstructive airway disease (COAD). A possible histamine generation by bacteria has been discussed. In the present work, histamine concentrations in native and incubated sputum of patients with COAD were determined. Histamine was assayed fluorimetrically after separation by HPLC. Histamine concentration in native sputum amounted to 10-1140 ng/ml. After 72 h incubation at 37 degrees C 100-20,700 ng/ml histamine was detected. A mean 26-fold increase in histamine content was observed. Heating of the sputum almost completely prevented the rise in histamine concentration during incubation. The same effect was achieved by adding an antibiotic to the sputum before incubation. Histamine content in sputum of patients with COAD decreased considerably after therapy with the antibiotic doxycycline. Histamine formation by bacteria may account considerably for the histamine concentration in sputum of patients with COAD.
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The influence of oral corticosteroid therapy (7.5 and 15 mg prednisolon/day for 8 days) on basophil releasability by antigens was investigated in a series of 16 patients with chronic obstructive airway disease. A significantly smaller histamine release was observed after the treatment. Different types of releasing curves were observed which mostly persisted after treatment.