Proof-of-concept study to establish an in situ method to determine the nature and depth of collagen changes in dentine using Fourier Transform Infra-Red spectroscopy after sodium hypochlorite irrigation.

AIM: To establish a method using Fourier Transform Infra-Red spectroscopy (FTIR) to characterize the nature and depth of changes in dentinal collagen following exposure to sodium hypochlorite (NaOCl) during root canal irrigation in an ex vivo model. METHODOLOGY: Fourier Transform Infra-Red spectroscopy was used to assess the changes in dentinal collagen when the root canal was exposed to NaOCl. The changes in dentinal collagen caused by NaOCl irrigation of root canals in transverse sections of roots, at 0.5 mm from the canal wall and 0.5 mm from the external root surface, were assessed by FTIR. The data were analysed using paired t-test with 5% significance level. RESULTS: Fourier Transform Infra-Red spectroscopy confirmed that NaOCl exposure caused alterations in the chemistry and structure of collagen in dentine. FTIR spectra obtained from dentine surfaces and dentine adjacent to root canals exposed to NaOCl, all consistently showed degradation and conformational change of the collagen structure. FTIR data from the ex vivo model showed that the depth of effect of NaOCl extended to at least 0.5 mm from the canal wall. CONCLUSION: In extracted human teeth, NaOCl caused changes in dentinal collagen that were measurable by FTIR. In an ex vivo model, the depth of effect into dentine extended at least 0.5 mm from the canal wall.

Fitness effects of new mutations in Chlamydomonas reinhardtii across two stress gradients.

Most spontaneous mutations affecting fitness are likely to be deleterious, but the strength of selection acting on them might be impacted by environmental stress. Such stress-dependent selection could expose hidden genetic variation, which in turn might increase the adaptive potential of stressed populations. On the other hand, this variation might represent a genetic load and thus lead to population extinction under stress. Previous studies to determine the link between stress and mutational effects on fitness, however, have produced inconsistent results. Here, we determined the net change in fitness in 29 genotypes of the green algae Chlamydomonas reinhardtii that accumulated mutations in the near absence of selection for approximately 1000 generations across two stress gradients, increasing NaCl and decreasing phosphate. We found mutational effects to be magnified under extremely stressful conditions, but such effects were specific both to the type of stress and to the genetic background. The detection of stress-dependent fitness effects of mutations depended on accurately scaling relative fitness measures by generation times, thus offering an explanation for the inconsistencies among previous studies.

Effects of antagonistic coevolution on parasite-mediated host coexistence.

Parasites can promote diversity by mediating coexistence between a poorer and superior competitor, if the superior competitor is more susceptible to parasitism. However, hosts and parasites frequently undergo antagonistic coevolution. This process may result in the accumulation of pleiotropic fitness costs associated with host resistance, and could breakdown coexistence. We experimentally investigated parasite-mediated coexistence of two genotypes of the bacterium Pseudomonas fluorescens, where one genotype underwent coevolution with a parasite (a virulent bacteriophage), whereas the other genotype was resistant to the evolving phages at all time points, but a poorer competitor. In the absence of phages, the resistant genotype was rapidly driven extinct in all populations. In the presence of the phages, the resistant genotype persisted in four of six populations and eventually reached higher frequencies than the sensitive genotype. The coevolving genotype showed a reduction in the growth rate, consistent with a cost of resistance, which may be responsible for a decline in its relative fitness. These results demonstrate that the stability of parasite-mediated coexistence of resistant and susceptible species or genotypes is likely to be affected if parasites and susceptible hosts coevolve.

Relative number of generations of hosts and parasites does not influence parasite local adaptation in coevolving populations of bacteria and phages.

A potential consequence of host-parasite coevolution in spatially structured populations is parasite local adaptation: local parasites perform better than foreign parasites on their local host populations. It has been suggested that the generally shorter generation times of parasites compared with their hosts contributes to parasites, rather than hosts, being locally adapted. We tested the hypothesis that relative generation times of hosts and parasites affect local adaptation of hosts and parasites, using the bacterium Pseudomonas fluorescens and a lytic phage as host and parasite, respectively. Generation times were not directly manipulated, but instead one of the coevolving partners was regularly removed and replaced with a population from an earlier time point. Thus, one partner underwent more generations than the other. Manipulations were carried out at both early and later periods of coevolutionary interactions. At early stages of coevolution, host and parasites that underwent relatively more generations displayed higher levels of resistance and infectivity, respectively. However, the relative number of generations that bacteria and phages underwent did not change the level of local adaptation relative to control populations. This is likely because generalist hosts and parasites are favoured during early stages of coevolution, preventing local adaptation. By contrast, at later stages manipulations had no effect on either average levels of resistance or infectivity, or alter the level of local adaptation relative to the controls, possibly because traits other than resistance and infectivity were under strong selection. Taken together, these data suggest that the relative generation times of hosts and parasites may not be an important determinant of local adaptation in this system.

Reductions in ethanol, phencyclidine, and food-maintained behavior by naltrexone pretreatment in monkeys is enhanced by open economic conditions.

RATIONALE: Previous results suggested that naltrexone had opioid-selective effects on behavior reinforced by orally delivered drugs and food. The present study explores the possibility that previous results were due to presentation of the reinforcers in a closed economy (all reinforcers earned by subjects) and that naltrexone's effect may be nonselective under conditions of an open economy (earned reinforcers supplemented by unearned). OBJECTIVES: The purpose of this experiment was to compare the effect of naltrexone on ethanol-, phencyclidine-(PCP), and food-reinforced responding under several open-economy conditions and compare them with those from a previous report using a closed economy. METHODS: Ethanol (8% w/v), PCP (0.25 mg/ml), and food were available under independent, concurrent, progressive-ratio (PR) schedules with water, and side positions were alternated daily. Three naltrexone doses (0.1, 0.3, and 1.0 mg/kg) were administered in a nonsystematic order for 5 days, with the 5-day pretreatment period serving as a control. Four economic conditions were compared: data for the closed economy were taken from a recently completed experiment using the same monkeys. The open-economy condition was varied by allowing free access to 1, 2 or 3 times the amount of drug or food that was earned during session later during a postsession time-out period. RESULTS: In an open economy, naltrexone nonselectively suppressed ethanol, PCP, and food-maintained behavior, in contrast to results in the previous study which used a closed economy, wherein naltrexone did not significantly suppress food- or PCP self-administration. As the economy for PCP, ethanol, and food became more open, the suppressant effects of naltrexone increased and, in many animals, behavioral measures decreased to zero. CONCLUSION: These results indicated that the economy under which drugs and food are self-administered is an important determinant of the effectiveness of naltrexone's ability to suppress drug- and food-reinforced behavior. The results also suggest that testing medications for drug abuse using a food control condition under a closed economy can bias the results toward a conclusion of selectivity of the treatment medication for drug-reinforced behavior.

An audit of doctor's management of patients with chest pain in the accident and emergency department.

In a series of 604 patients attending an accident and emergency department with chest pain, the decisions made by casualty officers about admission to the coronary care unit were compared with the retrospective opinions of experienced clinical assessors who knew the results of any subsequent investigations. Of the 119 patients whom the assessors judged should have been admitted to the coronary care unit, 14 (11.8 per cent) were judged to have been discharged in error. Of the 485 patients whom the assessors judged should not have been admitted to the coronary care unit, 32 (16 per cent) were judged to have been advised admission unnecessarily. Misinterpretation of the electrocardiographic results was apparently the reason for five of the 14 false negative errors and four of the 32 false positive errors. The median time that patients who were eventually admitted to the coronary care unit spent in the accident and emergency department was 78 min.

Pneumococcal serotypes in sputum isolates during acute respiratory illness in Edinburgh.

During the years 1978-83 serotyping was carried out on all sputum isolates of pneumococci obtained from patients in the chest wards of the City Hospital, Edinburgh. In 402 patients with acute respiratory illness the peak isolation rates occurred from January to April, and the serotype distribution was similar to that seen in previous UK studies, the commonest types being 3, 6, 9, 19, 23, and 8. The overall mortality rate was 8.7%, the serotype distribution in fatal cases reflecting the distribution of the whole group. The presence of mixed infection, predominantly with Haemophilus influenzae, was associated with a lower mortality rate of 3.5%. Nearly all patients (92%) were either elderly or had a chronic underlying disease and only one death occurred in a patient under 70 years who had no pre-existing disease. Of the pneumococcal serotypes isolated from the 292 patients with chronic chest disease, 82% are included in the new 23 valent pneumococcal vaccine and the efficacy of this needs to be assessed further in high risk patients.

Breathing patterns during sleep in patients with nocturnal asthma.

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.

Role of computed tomography in diagnosis of bronchiectasis.

Bronchograms and computed tomograms were performed in 27 patients who presented consecutively for bronchography with chronic sputum production. The films were reported separately by three consultant radiologists, who had been asked to give a diagnostic interpretation of the films for each bronchopulmonary segment. The reporting of bronchiectasis on computed tomograms was compared with that on bronchograms. The sensitivity and specificity of computed tomography at segmental level compared with bronchography was 66% and 92%, respectively. We conclude that computed tomography alone is not yet suitable for accurate characterisation and localisation of disease in patients in whom surgery is contemplated. Computed tomography may be useful in patients in whom bronchography is contraindicated and for monitoring progression of disease after initial combined computed tomography and bronchography.

Interpretation of bronchograms and chest radiographs in patients with chronic sputum production.

Bronchograms and plain chest radiographs of 27 patients with chronic sputum production were reported separately in random order and independently by two pulmonary radiologists to establish the diagnostic rate of each investigation and to assess interobserver variation. Both radiologists agreed on the presence of bronchiectasis on bronchography in 19 of 27 (70%) patients and in 94 of 448 (21%) bronchopulmonary segments. One radiologist only interpreted the films as showing bronchiectasis in a further two (7%) patients and 26 (6%) segments. There was more disagreement about the presence or absence of individual bronchographic abnormalities. Two main groups of patients with bronchiectasis were identified by bronchography: 11 with bronchiectasis alone and eight with bronchiectasis and bronchographic features suggestive of "chronic bronchitis". There was no clinical difference between these two groups. Plain chest radiographs were insensitive, being diagnostic (both radiologists agreeing) of bronchiectasis in only nine of 19 (47%) patients with definite bronchiectasis on bronchography.

Quantitative assessment of the value of spirometry.

To determine the value of simple spirometric measurements in the diagnostic assessment of breathless patients, doctors requesting such tests were asked to predict the likely ventilatory abnormality, expressing these pretest predictions as probabilities. Comparison of these pretest predictions with the test results allowed an analysis of the doctors' ability to identify lung function abnormalities and an assessment of the diagnostic usefulness of the test. Predictions and spirometric measurements were made in 123 patients. Doctors expressed preference for a particular spirometric category in 112 cases, of which 13 were predicted to have a restrictive defect, 77 were predicted to have an obstructive defect, and 22 were predicted to be normal. Spirometry showed that nine patients had a restrictive defect, 79 had an obstructive defect, and 24 had normal indices. The study showed that 61% of the tests gave a result that doctors predicted as being unlikely. The study also showed that doctors had difficulty in identifying the reversibility of airflow obstruction in patients in whom they correctly predicted obstruction. Spirometry fulfils a useful role in the diagnosis of breathless patients.

Sodium cromoglycate in nocturnal asthma.

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.

Almitrine improves oxygenation when both awake and asleep in patients with hypoxia and carbon dioxide retention caused by chronic bronchitis and emphysema.

Patients with chronic bronchitis and emphysema who are hypoxic when awake become more hypoxic during sleep, with a further rise in their preexisting pulmonary hypertension. Almitrine, a respiratory stimulant, improves arterial blood gas tensions in such patients when they are awake. We have used a double-blind, placebo-controlled, cross-over study to compare the effects of 50 mg almitrine given orally twice a day for 14 days on oxygen saturation (SaO2), respiratory movements, and sleep quality in 9 patients with hypoxic chronic bronchitis and emphysema (FEV1, 0.4 to 1.0 L; PaO2, 51 +/- (SEM) 2 mmHg; PaCO2, 49 +/- 1 mmHg). Almitrine improved arterial blood gas tensions when awake, mean PaO2 rising by 8 mmHg (p less than 0.001) and PaCO2 falling by 4 mmHg (p less than 0.01). Almitrine improved nocturnal oxygenation, mean SaO2 when awake rising from 83 +/- 4% to 89 +/- 3% (p less than 0.01), and the lowest SaO2 during sleep rising on average from 65 +/- 6% to 77 +/- 3% (p less than 0.02). The number of hypoxemic episodes (SaO2 falling by greater than or equal to 10% from the preceding stable baseline during sleep) and the time when SaO2 was below 80% (135 +/- 53 versus 46 +/- 35 min; p less than 0.01) also improved. Almitrine did not improve sleep quality. We conclude that almitrine improves arterial gas tensions when awake and reduces the frequency and severity of nocturnal hypoxemia without impairing sleep quality in patients with chronic bronchitis and emphysema who are both hypoxemic and hypercapnic when awake.(ABSTRACT TRUNCATED AT 250 WORDS)

Right ventricular performance during exercise in chronic obstructive pulmonary disease. The effects of oxygen.

Radionuclide ventriculography allows non-invasive assessment of right ventricular performance. This study has confirmed that there is a modest reduction in right ventricular ejection fraction (RVEF) in patients with chronic obstructive pulmonary disease (COPD), as compared to normal subjects. However, occult right ventricular dysfunction also becomes apparent in these patients during exercise. The change in RVEF during exercise is related to the corresponding fall in arterial oxygen saturation in patients with COPD. Oxygen improves the response of the right ventricle to exercise, although the mechanism remains unclear. Long-term oxygen therapy, in patients with respiratory failure, does not appear to have any significant effect on RVEF.

Pneumococcal serotyping and antigen detection in pneumococcal pneumonia of adults.

A retrospective study of 125 patients presenting to the City Hospital, Edinburgh, with proven pneumococcal pneumonia showed that pneumococcus serotype 3 remains the most prevalent and that since 1970 the distribution of serotypes has remained virtually constant. The frequency of diagnosing pneumococcal pneumonia is increased by the use of countercurrent immuno-electrophoresis (CIE) of sputum. In this series, 25 per cent of patients with negative sputum culture but radiological evidence of pneumonia, were diagnosed by means of this method, which was overall more helpful in making the diagnosis than blood cultures. All nine deaths in this series were in those over 65 years of age.