Serum eosinophil cationic protein (ECP) as a mediator of inflammation in acute asthma, during resolution and during the monitoring of stable asthmatic patients treated with inhaled steroids according to a dose reduction schedule.

OBJECTIVE AND DESIGN: The main objective was to establish the level of serum ECP in a group of adult asthmatic patients with acute exacerbation and the following resolution and in another group of adult, stable asthmatic patients during reduction of inhaled steroids. SUBJECTS AND TREATMENT: Acute group: Twenty-one asthmatic patients admitted to the asthma clinic with acute deterioration of their asthma were set on oral steroids which were reduced to 0 within one week. Reduction group: Forty-four stable asthmatic patients on maintenance inhaled steroids were included and, on the basis of their peak expiratory flow (PEF) values, adjustments in the doses of steroids were made. CONTROL GROUP: Twenty stable asthmatics on a constant dose of inhaled steroids were enrolled as controls. METHODS: All patients registered daily PEF measurements and spirometry was performed at each visit. Blood samples were drawn and analysed for eosinophil cationic protein (ECP), myeloperoxidase (MPO), eosinophils and neutrophils. RESULTS: ECP was low and within the normal range for all three groups at study entry. (Acute group = 8.4 microg/l, reduction group = 3.7 microg/l and control group = 4.6 microg/l). Nevertheless, the value in the acute group was significantly higher than in the control group (p=0.005). The levels in the acute group decreased significantly (p=0.004) after one week on oral steroids. No significant changes in ECP were observed in the reduction group or in the control group during the follow-up period. The lung function was low in the acute group at inclusion, forced expiratory volume in one second (FEV1)=47.1% of predicted, and increased significantly during the treatment period (p = 0.006). The patients in the reduction- and control group showed small variations in lung function during the whole study, FEV1 >70% and PEF > 80% of predicted, respectively. No correlation between atopy and ECP was found in the patients irrespective of the stage of disease. CONCLUSIONS: This study suggests that the resolution of acute asthma exacerbations during treatment could be followed using ECP determinations. In stable asthmatics on inhaled steroids and with normal ECP levels, a dose reduction could be indicated. A longer period after tapering off steroids is proposed to confirm the benefit of ECP measurements for controlling asthma.

Systemic effects of a short course of betamethasone compared with high-dose inhaled budesonide in early childhood asthma.

Forty children aged 1-3 y completed a placebo-controlled study on the effects of 10 d of inhaled budesonide for asthma caused by respiratory tract infection. The effects on symptoms were significantly better in the active than in the placebo group. In 20 of these children the systemic effects of high-dose inhaled budesonide for 10 d and the effect of a 3-d course of oral betamethasone on asthma exacerbation were evaluated. Systemic effects were evaluated by measuring morning cortisol in serum and urine, and the bone markers osteocalcin, ICTP (the C-terminal telopeptide region of type I collagen) and PIIINP (an N-terminal propeptide of type III procollagen) in serum before and at the end (d 7-10) of treatment (1600 microg budesonide d(-1) for 3 d and 800 microg for 7 d). In 9 children, measurements were taken on d 3 of a 3-d course of betamethasone (6, 4 and 2 mg) for asthma exacerbation and 14 d later. There were no signs of systemic effects after 7-10 d of budesonide. After 3 d of betamethasone, serum cortisol decreased from a median of 263 to 26 nmol l(-1), urine cortisol/creatinine from 19.9 to 7.2 nmol l(-1), osteocalcin from 31.4 to 5.5 microg l(-1), ICTP from 19.4 to 8.5 microg l(-1) and PIIINP from 12.3 to 5.9 microg l(-1). Two weeks later, the levels were back to normal. In conclusion, short courses of oral betamethasone have pronounced systemic effects, whereas 10 d of high doses of budesonide do not produce significant systemic effects.

Circadian rhythm of serum interleukin-6 in rheumatoid arthritis.

OBJECTIVES: To test the hypothesis of a diurnal variation in circulating levels of interleukin-6 (IL-6) and/or tumour necrosis factor-alpha (TNF-alpha) in rheumatoid arthritis and other inflammatory connective tissue diseases. METHODS: Serum levels of IL-6 and TNF-alpha were measured at three hour intervals from 7:30 to 22:30 in 48 patients with different rheumatic diseases as well as ten healthy controls. In four of the patients with rheumatoid arthritis, serum IL-6 levels were measured before and after one week of treatment with prednisolone 15-20 mg daily. RESULTS: IL-6 and TNF-alpha could not be detected in serum from healthy controls. However, serum IL-6 levels were substantially increased in patients with rheumatoid arthritis. Furthermore, patients with rheumatoid arthritis showed a statistically significant circadian variation in levels of IL-6. Peak values appeared in the morning and low values in the afternoon and evening. In contrast, levels were low and stable in other connective tissue diseases. Levels of TNF-alpha were low in patients with rheumatoid arthritis and high in patients with other connective tissue diseases, but without circadian rhythm. After treatment with prednisolone, levels of serum IL-6 decreased significantly, but the circadian rhythm remained. CONCLUSIONS: The circadian rhythm of circulating IL-6 might correspond to the circadian rhythm of symptoms in rheumatoid arthritis. The diurnal variation of IL-6, and possibly other cytokines, might explain the conflicting results previously reported on the inter-relationship between circulating IL-6 levels and disease activity in rheumatoid arthritis.

The aerobic and anaerobic microflora of the gastric remnant more than 15 years after Billroth II resection.

The bacteriology of the gastric remnant contents was examined in 150 patients 15-20 years after Billroth II resection for duodenal ulcer disease. Samples of gastric contents were aspirated through a gastroscope, and aerobic and anaerobic microflora were cultured and analyzed semiquantitatively. All patients but one had bacterial growth, with a mean number of 6.8 strains per remnant. One third of the bacterial strains were anaerobic, and many of them had their normal habitat in the colon. The role played by bacteria of the gastric remnant in the etiology of mucosal pathology and gastric remnant disease is discussed.

Fecal bacterial flora of four nordic population groups with diverse incidence of large bowel cancer.

Fecal samples were collected and biologically examined from 4 population groups, exhibiting a 3-fold range in colon cancer incidence, in Denmark and Finland. Carrier rates and counts per gram feces of several aerobic as well as anaerobic genera, including nuclear dehydrogenase-producing clostridia, were calculated. The results obtained with the described method did not confirm a relationship between colon cancer incidence and carrier rates of intestinal bacteria.

The clinical importance of anaerobic bacteria in wound infections after gastrointestinal surgery.

Wound cultures from 54 patients with infections after gastrointestinal surgery were examined. Cultures from wounds after surgery on the upper gastrointestinal tract grew few organisms, mainly aerobic gram-positive cocci. Culture from wounds on the lower gastrointestinal tract grew strains of bacteria, aerobic and anaerobic gram-negative rods dominating. Indirect immunofluorescence studies on acute and convalescent phase sera showed significant immune response against Bacteroides fragilis in a majority of cases. Immune response against anaerobic cocci was seldom found. Very high antibody titres against Clostridium perfringens were often found, both in patients' and control sera.

Antibody response in thirteen patients with Bacteroides fragilis infections.

13 patients with Bacteroides fragilis infections were studied for antibody response against the infecting strain using indirect immunofluorescence (IFL), passive hemagglutination (HA) and tube agglutination (TA). With indirect IFL significant titre changes in IgG were found in 12/13 cases, in IgA in 8/13 and in IgM in 4/13 cases. With passive HA significant titre changes were found in 11/13 cases and with TA in 6/11 cases. The rise in antibody titre was fast and persisted for a long time in most cases. Of the methods used the indirect IFL was the most convenient for clinical use.

The possible role of anaerobic bacteria in the aetiology of non-gonococcal urethritis in men.

Men with non-gonococcal urethritis (NGU) were divided into two groups and treated with either lymecycline or tinidazole; anaerobic cultures were performed before and after treatment. Neither treatment affected the anaerobic flora. However, the men treated with lymecycline were relieved of symptoms and signs, while those treated with tinidazole were not. The anaerobic bacteria found are considered normal inhabitants of the urethral tract and without significance in the aetiology of NGU.

Isolation and characterization of two protease-producing mutants from Staphylococcus aureus.

Two mutants with increased protease production were isolated after nitrosoguanidine treatment of Staphylococcus aureus 8325N. The wild type produces low amounts of extracellular proteolytic activity. The enzyme was inducible and could only be detected if casein or preferably skim milk powder was used as inducer. The optimal pH, salt concentration, and media for enzyme production were determined. The mutants differed from the wild type in several phenotypic characters. The pattern of extracellular deoxyribonuclease and alkaline phosphatase differed between the mutants and the wild type. Several carbohydrates such as lactose, galactose, and mannitol were not utilized by the mutants, probably owing to a block in the uptake. Glucose could, however, be utilized by the mutants. Reversion frequency to wild type with regard to carbohydrate utilization was spontaneously high, and all revertants regained the parental pattern irrespective of the carbohydrate used for selection. The results suggest that a single locus may control the excretion of extracellular enzymes and carbohydrate uptake in S. aureus.