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1.  Characterisation of an oxidative response inhibitor produced by Streptococcus pneumoniae. 
Thorax  1994;49(7):676-683.
BACKGROUND--Pneumonia caused by infection with Streptococcus pneumoniae is still a major clinical problem. Reactive oxygen species contribute to the killing of these bacteria by polymorphonuclear leucocytes (PMNs). Defence mechanisms of Str pneumoniae which counter reactive oxygen species are characterised. METHODS--PMNs were stimulated with phorbol myristate acetate (PMA) in the presence and absence of Str pneumoniae and supernatants from them, and superoxide (O2-) production was measured by the reduction of ferricytochrome c. RESULTS--Streptococcus pneumoniae, but not Klebsiella pneumoniae or Staphylococcus aureus, inhibited PMA stimulated superoxide production by PMNs. Washed PMNs which had been preincubated with Str pneumoniae autolysis phase supernatants also exhibited depressed H2O2 production in response to PMA. The inhibitory activity was not attributable to non-specific cytotoxicity as assessed by release of the cytoplasmic enzyme lactate dehydrogenase, nor did the supernatants inhibit PMA stimulated degranulation of PMNs. Fractionation of the autolysis phase supernatants revealed inhibitory activity in both the fractions greater than and less than 10 kD. Like pneumolysin the inhibitory activity was heat sensitive. However, both a parent and pneumolysin negative mutant Str pneumoniae, and autolysis phase supernatants from them, inhibited PMN superoxide production. Antisera to pneumolysin failed to abrogate the inhibitory effect of intact Str pneumoniae or autolysis phase supernatants from types 1 or 14 Str pneumoniae. CONCLUSIONS--The inhibitory effect of Str pneumoniae on the respiratory burst of PMNs is not shared by two other common lung pathogens. The existence of a novel inhibitor of the PMN respiratory burst, distinct from pneumolysin, has been demonstrated. The inhibitor is specific for the respiratory burst and is active both in the logarithmic phase of growth and during autolysis.
PMCID: PMC475056  PMID: 8066562
2.  Interference with the oxidative response of neutrophils by Streptococcus pneumoniae. 
Thorax  1993;48(4):364-369.
BACKGROUND--Pneumococcal infections are still a major clinical problem. Polymorphonuclear leucocytes (neutrophils) are considered to have a key role in the host's defence against Streptococcus pneumoniae but the mechanisms by which they kill the pneumococcus remain unclear. As reactive oxygen species are regarded as a major antimicrobial defence of phagocytes an attempt has been made to establish their role in the response of neutrophils to S pneumoniae. METHODS--S pneumoniae isolated from patients with bacteraemic pneumococcal pneumonia were incubated with neutrophils in suspension and superoxide production was measured by reduction of ferricytochrome c. RESULTS--S pneumoniae did not stimulate superoxide production alone or in the presence of normal human serum. Spontaneous superoxide production by neutrophils was actually abrogated by S pneumoniae, as was the powerful respiratory burst stimulated by phorbol myristate acetate. This phenomenon depended on both the dose and the viability of the bacteria. With S pneumoniae in the logarithmic phase of growth inhibitory activity was confined to the organisms themselves but with organisms undergoing autolysis it was also present in filtered supernatants, suggesting that the inhibitory activity can be attributed to a factor released during autolysis. CONCLUSIONS--S pneumoniae can interfere with the respiratory burst of neutrophils. This property may help to explain the pathogenicity of the organism.
PMCID: PMC464434  PMID: 8390109
3.  ABC of sleep disorders. Nocturnal asthma. 
BMJ : British Medical Journal  1993;306(6886):1189-1192.
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PMCID: PMC1677647  PMID: 8499828
4.  Is nocturnal asthma caused by changes in airway cholinergic activity? 
Thorax  1988;43(9):720-724.
A randomised, double blind, placebo controlled crossover trial of high dose nebulised ipratropium was carried out in 10 asthmatic patients with documented nocturnal bronchoconstriction. Patients received nebulised saline or ipratropium 1 mg at 10 pm and 2 am on two nights. Absolute peak flow (PEF) rates were higher throughout the night after the patients had received ipratropium (at 2 am, for example, mean (SEM) PEF was 353 after ipratropium and 285 l/min after placebo). The fall in PEF overnight, however, was similar with ipratropium and placebo. Patients were given a further 1 mg nebulised ipratropium at 6 am on both nights. There was a significant overnight fall in PEF on the ipratropium night even when comparisons were made between the times that maximal cholinergic blockade would be expected, PEF falling between 11.30 pm and 7.30 am from 429 to 369 l/min. The percentage increase in PEF, though not the absolute values, was greater after ipratropium at 6 am than at 10 pm. These results confirm that ipratropium raises PEF throughout the night in asthmatic patients, but suggest that nocturnal bronchoconstriction is not due solely to an increase in airway cholinergic activity at night.
PMCID: PMC461462  PMID: 2973665
5.  Breathing patterns during sleep in patients with nocturnal asthma. 
Thorax  1987;42(8):600-603.
Breathing patterns early and late in the night, at the same sleep stage, were compared in six healthy subjects and 15 adults with nocturnal asthma, to try to identify changes of overnight bronchoconstriction, and breathing patterns at different sleep stages, to see whether there were changes related to sleep stages that were indicative of bronchoconstriction. Despite an average 31% fall in FEV1 overnight in the patients with asthma, neither breathing frequency nor expiratory time, which might be expected to change during bronchoconstriction, was different early in the night from late in the night, nor did they differ between sleep stages. There was no evidence of asynchronous movement of the chest and abdomen in any patient. This study did not identify any abnormality of breathing pattern that would indicate the development of nocturnal asthma without the need to awaken the patient.
PMCID: PMC460860  PMID: 3509951
6.  Effect of sleep deprivation on overnight bronchoconstriction in nocturnal asthma. 
Thorax  1986;41(9):676-680.
Nocturnal cough and wheeze are common in asthma. The cause of nocturnal asthma is unknown and there is conflicting evidence on whether sleep is a factor. Twelve adult asthmatic subjects with nocturnal wheeze were studied on two occasions: on one night subjects were allowed to sleep and on the other they were kept awake all night, wakefulness being confirmed by electroencephalogram. Every patient developed bronchoconstriction overnight both on the asleep night, when peak expiratory flow (PEF) fell from a mean (SE) of 418 (40) 1 min-1 at 10 pm to 270 (46) 1 min-1 in the morning, and on the awake night (PEF 10 pm 465 (43), morning 371 (43) 1 min-1). The morning values of PEF were, however, higher (p less than 0.1) after the awake night and both the absolute and the percentage overnight falls in PEF were greater when the patients slept (asleep night 38% (6%), awake night 20% (4%); p less than 0.01). This study suggests that sleep is an important factor in determining overnight bronchoconstriction in patients with nocturnal asthma.
PMCID: PMC460429  PMID: 3787554
7.  Do asthmatics suffer bronchoconstriction during rapid eye movement sleep? 
Many patients with asthma are troubled by nocturnal wheeze. The cause of this symptom is unknown, but sleep is an important factor. A study was carried out to determine whether nocturnal bronchoconstriction is related to any specific stage of sleep. Eight asthmatics with nocturnal wheeze and eight control subjects performed forced expiratory manoeuvres immediately after being woken from rapid eye movement (REM) or non-REM sleep, wakings being timed to differentiate temporal effects from those related to the stage of sleep. The control subjects showed no significant temporal bronchoconstriction or bronchoconstriction related to the stage of sleep. All patients showed bronchoconstriction overnight, the mean peak expiratory flow rate falling from 410 (SEM 50) 1/min before sleep to 186 (49)1/min after sleep. After the patients had been woken from REM sleep the forced expiratory volume in one second was on average 300 ml lower (p less than 0.02) and peak expiratory flow rate 45 1/min lower (p less than 0.03) than after they had been woken from non-REM sleep. As wakenings from REM sleep were 21(8) minutes later in the night than those from non-REM sleep multivariate analysis was performed to differentiate temporal effects from those related to the stage of sleep. This showed that the overnight decreases in forced expiratory volume in one second and peak expiratory flow rate were significantly related both to time and to REM sleep. This study suggests that asthmatics may suffer bronchoconstriction during REM sleep.
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PMCID: PMC1340176  PMID: 3085766
8.  Chronic nicotine ingestion and atrial fibrillation. 
British Heart Journal  1985;54(2):222-223.
Paroxysmal atrial fibrillation occurred in a fit 35 year old man who consumed large doses of nicotine chewing gum (Nicorette Leo) over a prolonged period.
PMCID: PMC481883  PMID: 4015933
11.  Nonoxidative microbicidal activity in normal human alveolar and peritoneal macrophages. 
Infection and Immunity  1987;55(7):1635-1640.
Although Toxoplasma gondii multiplies within normal murine alveolar and peritoneal macrophages, it is killed by normal rat alveolar and peritoneal macrophages. The killing by rat macrophages is by a nonoxidative mechanism. Studies on normal human alveolar macrophages have reported disparate results in regard to their ability to inhibit or kill T. gondii. We considered it of interest to explore further the effect of normal human alveolar and peritoneal macrophages on T. gondii. Unstimulated alveolar macrophages from each of seven individuals demonstrated a marked ability to kill or inhibit multiplication of T. gondii in vitro (e.g., the number of parasites per 100 alveolar macrophages was 31 at time zero and 2 at 18 h, whereas this value increased from 37 at time zero to 183 at 18 h in murine macrophages assayed in parallel). In quantitative assays of superoxide, alveolar macrophages released a substantial amount of superoxide when exposed to phorbol myristate acetate or to candidae. In contrast, alveolar macrophages incubated with T. gondii released no more superoxide than when in medium alone. Scavengers of superoxide anions, hydrogen peroxide, singlet oxygen, and hydroxyl radicals failed to inhibit killing of T. gondii by alveolar macrophages. Peritoneal macrophages from each of six normal women undergoing laparoscopy killed T. gondii in vitro; results of quantitative superoxide assays and scavenger experiments demonstrated that no oxidative burst was triggered in these macrophages by exposure to T. gondii. These data indicate that normal human alveolar and peritoneal macrophages can kill an intracellular parasite by nonoxidative mechanisms and suggest that these mechanisms are important in inhibition or killing of other opportunistic intracellular pathogens.
PMCID: PMC260570  PMID: 3036709
12.  Ketotifen and nocturnal asthma. 
Thorax  1983;38(11):845-848.
Patients with asthma often wheeze at night and they also become hypoxic during sleep. To determine whether ketotifen, a drug with sedative properties, is safe for use at night in patients with asthma, we performed a double blind crossover study comparing the effects of a single 1 mg dose of ketotifen and of placebo on arterial oxygen saturation (SaO2), breathing patterns, electroencephalographic (EEG) sleep stage, and overnight change in FEV1 in 10 patients with stable asthma. After taking ketotifen, the patients slept longer and their sleep was less disturbed than after taking placebo, true sleep occupying 387 (SEM 8) minutes after ketotifen and 336 (19) minutes after placebo (p less than 0.02). On ketotifen nights the patients had less wakefulness and drowsiness (EEG sleep stages 0 and 1) and more non-rapid eye movement (non-REM) sleep than on placebo nights, but the duration of REM sleep was similar on the two occasions. Nocturnal changes in SaO2, the duration of irregular breathing, and overnight change in FEV1 were unaffected by ketotifen.
PMCID: PMC459674  PMID: 6359563
13.  Sodium cromoglycate in nocturnal asthma. 
Thorax  1986;41(1):39-41.
To investigate whether mast cell degranulation was important in producing nocturnal asthma, the effect of a single high dose of nebulised sodium cromoglycate on overnight bronchoconstriction, oxygen saturation, and breathing patterns in eight patients with nocturnal wheeze was examined. The study took the form of a double blind placebo controlled crossover comparison. Treatment with cromoglycate did not reduce the overnight fall in FEV1 or FVC, although it was associated with improved nocturnal oxygenation. This study suggests that mast cell degranulation may not be important in the pathogenesis of nocturnal asthma.
PMCID: PMC460250  PMID: 3085257
14.  Arterial oxygenation during sleep in patients with right-to-left cardiac or intrapulmonary shunts. 
Thorax  1983;38(5):344-348.
We have studied arterial oxygen saturation (SaO2), breathing patterns, and electroencephalographic (EEG) sleep stage during nocturnal sleep in six patients with right-to-left cardiac or intrapulmonary shunts and six patients with chronic bronchitis and emphysema, chosen because they were equally hypoxaemic when awake (SaO2 during wakefulness: bronchitis 74-90%, mean 83%; shunt 77-89%, mean 83%). The patients with bronchitis had far greater falls in SaO2 when asleep than those with shunts (maximum fall in SaO2 during sleep: bronchitis 14-47%, mean 29%; shunt 5-10%, mean 8%; p less than 0.01). Significant episodes of hypoxaemia (defined as SaO2 falls greater than 10%) occurred in all six bronchitic patients, from once to seven times per night, but in none of the patients with shunts (p less than 0.05). Twenty-four of the 27 episodes of hypoxaemia occurred in rapid-eye-movement (REM) sleep and 24 were associated with hypopnoea. The two groups of patients had similar EEG sleep patterns and the same amount of hypopnoea during sleep. Thus the level of arterial oxygenation when the patient is awake is not the sole determinant of the degree of nocturnal hypoxaemia; the pathological process is also important.
PMCID: PMC459555  PMID: 6879482

Results 1-16 (16)