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Biomedical subjects

P L Haslam

Publications and source records attributed to P L Haslam.

At least 55 records · Page 3Linked to original sources
PubMed1987

Development of acute lung injury after the combination of intravenous bleomycin and exposure to hyperoxia in rats.

Pulmonary toxicity is an important adverse effect of bleomycin treatment. Very little is known of the mechanisms underlying the development of lung injury, especially after intravenous administration, or how it can be modulated. In this study acute lung injury induced by bleomycin has been examined in rats by assessment of alveolar lavage cell profiles, histological examination, and measurement of the total pulmonary extravascular albumin space. Intratracheal instillation of bleomycin 1.5 mg resulted in a severe pneumonitis with influx of inflammatory cells into the alveoli as assessed by alveolar lavage, oedema of the alveolar walls, and up to an eight fold increase in the total pulmonary extravascular albumin space, maximal at 72 hours. Intravenous bleomycin 0.15-5 mg produced no detectable injury when assessed in these ways. Exposure to hyperoxia (40-90%) after intravenous bleomycin, however, induced lung injury similar to that produced by intratracheal bleomycin. A much more severe injury followed administration of intravenous bleomycin after an exposure to hyperoxia, which itself resulted in lung injury; but lung injury was still detectable after bleomycin when the exposure to hyperoxia was insufficient to induce changes in control animals. Lung injury was not observed when the exposure to hyperoxia preceded bleomycin treatment. These results indicate the importance of oxygen in the pathways leading to acute lung injury following intravenous bleomycin. We conclude that exposure to oxygen might induce lung injury during and after bleomycin treatment, and suggest that in these circumstances oxygen therapy should be kept to a minimum.

Animals↗
PubMed1987

The value of serial bronchoalveolar lavages in assessing the clinical progress of patients with cryptogenic fibrosing alveolitis.

This study tested the hypothesis that changes in bronchoalveolar lavage (BAL) inflammatory cell profiles reflect the clinical progress of patients with cryptogenic fibrosing alveolitis (CFA) when followed for substantial periods of time with or without any form of treatment. Two or more bronchoalveolar lavages (mean, 3; maximum, 5) were performed on each of 32 patients who were followed for periods as long as 7 yr (mean, 2.5 yr, median, 4 yr). The majority were studied before and during treatments with prednisolone alone or with prednisolone and cyclophosphamide. A total of 90 lavages were performed, and the changes in BAL inflammatory cell percentage counts were compared with defined categories of clinical progress. At initial lavage, 97% of the patients had an increased percentage of at least 1 BAL cell type. On follow-up, 12 patients showed definite and sustained clinical improvement, and their serial lavage cell counts tended to return towards normal. Falls in neutrophils were significant in patients responding to prednisolone, whereas falls in eosinophils were significant in those responding to cyclophosphamide. By contrast, in patients who failed to improve, neutrophil and eosinophil counts tended to remain elevated. However, several nonresponders appeared to have clinically stable disease, demonstrating that persisting granulocytes are not necessarily paralleled by clinical deterioration. Consecutive BAL cell counts in the pair of samples before and after introduction of prednisolone showed no overall change in any lavage cell type to suggest that the drug has a general effect independent of clinical progress. A similar comparison for cyclophosphamide showed falls in eosinophil percentage counts, but these were mainly responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchi↗
PubMed1987

Mast cells, atypical lymphocytes, and neutrophils in bronchoalveolar lavage in extrinsic allergic alveolitis. Comparison with other interstitial lung diseases.

Bronchoalveolar lavage (BAL) samples from exposed patients with extrinsic allergic alveolitis (EAA) contained mast cells in increased numbers in addition to lymphocytes. The counts rarely exceeded 0.5% in sarcoidosis, cryptogenic fibrosing alveolitis, or asbestosis or in control samples, but they were as much as 10-fold higher in EAA (p less than 0.001). Higher concentrations of histamine were demonstrated in EAA BAL-cell lysates, and histamine was released from cells challenged with anti-IgE. Electron microscopic examination confirmed that the cells were mast cells that differed from mast cells in dermal connective tissue and alveolar interstitial tissue but resembled bronchial subepithelial tissue mast cells in showing more features suggestive of activation. However, they showed more marked degranulation, and many were young. By light microscopy, they also resembled "mucosal" rather than "connective" tissue mast cells since granule staining was prevented by formaldehyde. Mast cell counts fell to normal after removal of patients from exposure, but lymphocyte increases, including atypical "blast" forms, persisted despite clinical recovery. Neutrophils were also increased before, but rarely after, removal. We suggest that EAA may provide an example of a human disease to support recent evidence that some delayed hypersensitivity disorders involve mast cells as well as lymphocytes.

Alveolitis, Extrinsic Allergic↗
PubMed1987

The effects of iron and desferrioxamine on the lung injury induced by intravenous bleomycin and hyperoxia.

The development of acute lung injury in rats following the intravenous injection of bleomycin was assessed by measuring the total pulmonary extravascular albumin space. Intravenous bleomycin alone produced no evidence of lung injury, yet when combined with a simultaneous exposure to hyperoxia or simultaneous tracheal instillation of ferric iron or ascorbate a severe lung injury evolved. Neither ferric iron or ascorbate alone produced lung injury when assessed in this manner, and ferrous iron, ferritin and haemoglobin did not potentiate bleomycin induced lung injury. A continuous subcutaneous infusion of desferrioxamine enhanced hyperoxia induced lung injury, and had no modulating effect on the lung injury produced by combined intravenous bleomycin and hyperoxia. These results indicate that ferric iron can potentiate bleomycin induced lung injury, and that the metal chelator desferrioxamine can have adverse effects on the development of acute lung injury.

Animals↗
PubMed1986

Corticosteroid treatment in pulmonary sarcoidosis: do serial lavage lymphocyte counts, serum angiotensin converting enzyme measurements, and gallium-67 scans help management?

Thirty two patients with persisting pulmonary sarcoidosis fulfilling defined criteria for treatment were managed according to a standard clinical protocol. In this an attempt was made to achieve and maintain maximal radiographic and physiological improvement with individually titrated doses of corticosteroids. Lavage cell counts, serum angiotensin converting enzyme (SACE) determinations, and gallium-67 scans were planned at standard intervals but were not used in management decisions. The study analysed serial measurements in relation to changes in the clinical measurements. Twelve patients' radiographs showed complete clearing, seven cleared partially, and 13 had partial clearing with evidence of fibrosis. There was no predictive value in the initial lavage lymphocyte counts or the SACE or gallium measurements. Notably, in seven patients, substantial radiographic improvement was observed when the initial lavage lymphocyte counts were normal. Higher initial lavage neutrophil counts (p less than 0.02), higher initial radiographic profusion scores (p less than 0.02), and lower vital capacity (p less than 0.01) and carbon monoxide transfer factor (p less than 0.05) were related to incomplete clearing. A repeat study of the patients when their radiograph had cleared maximally showed that the levels of lavage lymphocytes, SACE, and gallium tended to fall, but frequently remained raised even in the presence of a normal radiograph or vital capacity or both. On the other hand, however, most of the patients with a normal lavage lymphocyte count showed persisting abnormality of the radiograph, lung function measurements, SACE, and gallium scan (or of at least one of these indices). The interrelationships between changes in clinical indices (radiograph, vital capacity, and transfer factor) and in lavage lymphocyte counts, SACE, and gallium scans showed that concordance was fairly poor in each comparison; lavage lymphocytes showed a greater major discordance than did the other pairs of measurements. Symptom free patients with normal or stable radiographic appearances have been followed for many months and have shown no clinical deterioration despite abnormal lavage lymphocyte counts, SACE, and gallium scans. Radiographic relapse, within the criteria defined, was seen in only four patients during the study; this was reflected in the gallium counts in three and in SACE and lavage lymphocyte counts measurements in two. It is concluded that serial lavage lymphocyte counts, serum angiotensin converting enzyme measurements, and gallium-67 scans are not consistently more sensitive methods by which to monitor patients with sarcoidosis during treatment than are serial measurements of high quality radiographs and results of standard lung function tests.

Adult↗
PubMed1986

Bronchoalveolar lavage in patients with interstitial lung diseases: side effects and factors affecting fluid recovery.

One hundred and seventy patients with interstitial lung diseases undergoing bronchoalveolar lavage (BAL), were contrasted with 51 patients undergoing fibreoptic bronchoscopy alone to define the factors which predispose to post-lavage side-effects. Transient post-bronchoscopy fall in the peak expired flow (PEF) greater than or equal to 20% occurred in both groups (24% and 23% respectively), and thus was probably related to the bronchoscopy procedure. Post-lavage pyrexia (greater than or equal to 1 degree C) occurred only in the patients undergoing BAL (26%), p less than 0.001. Only 4% with pyrexia required antibiotics, and only 2% with falls in PEF needed bronchodilator therapy. The only significant clinical association was more frequent pyrexia in patients on treatment with prednisolone, particularly in women (p less than 0.01). Pyrexia was also associated with higher lavage fluid introduction volumes (greater than 240 ml). Side effects did not relate to the percentages of lavage fluid recovered, although smokers had lower recoveries and, recoveries tended to be higher in sarcoidosis than cryptogenic fibrosing alveolitis. Serial lavages in 25 patients caused no significant increase in side effects.

Adult↗
PubMed1985

Chronic pulmonary sarcoidosis: relationship between lung lavage cell counts, chest radiograph, and results of standard lung function tests.

Thirty three consecutive untreated patients with pulmonary sarcoidosis, confirmed histologically or by Kveim test, were investigated to correlate cell counts in bronchoalveolar lavage fluid with clinical features, the chest radiograph, and results of lung function tests. A persistently abnormal radiograph had been observed for one year or more in 26 (79%) and for two years or more in 20 (61%), but only 24% had dyspnoea. Twenty (61%) of 33 patients showed an increased percentage of lymphocytes in bronchoalveolar lavage fluid, although only eight (24%) exceeded 28%. A moderate increase of neutrophils, up to 12%, was found in 14 (42%). Lymphocyte percentage counts were higher in the group of patients without evidence of radiographic contraction suggesting fibrosis, and this contrasted with higher percentage neutrophil counts in those with contraction. There was also a correlation between the percentages of neutrophils and increasing radiographic profusion scores (p less than 0.001), suggesting that neutrophils may reflect the severity of the parenchymal legions as well as fibrotic distortion, and an inverse correlation with vital capacity (p less than 0.001) and transfer factor (TLCO) (p less than 0.1 greater than 0.05). No significant correlation was found between the lymphocyte counts and radiographic profusion scores, vital capacity or TLCO; but it was noted that all eight patients with high lymphocyte counts (greater than 28%) had radiographic profusion scores less than 12. This study shows that, especially in sarcoidosis with more extensive radiographic shadows of long duration, bronchoalveolar lavage neutrophils may be important as well as lymphocytes in clinical assessment of "activity" of disease. These observations are important because they throw doubt on whether the lavage lymphocyte count alone can be used as an indicator of the need to start corticosteroid treatment.

Adult↗
PubMed1985

Numerical and functional alterations in circulatory lymphocytes in cigarette smokers.

Simultaneous numerical and functional studies of circulatory lymphocytes were undertaken in healthy non-smoking and cigarette-smoking volunteers. The smokers all had light to moderate histories of less than 50 pack years. By contrast with non-smokers (n = 32), the smokers (n = 14) had a significant increase in the total number of lymphocytes, surface immunoglobulin bearing (sIg+) cells, total T-cells (T3+) and T helper-inducer cells (T4+), and a trend of increase in T suppressor-cytotoxic cells (8+). These changes differ from those in heavy smokers who have been reported to show significantly increased T suppressor-cytotoxic but significantly decreased T helper-inducer cells. Although the proportions of T-cell subsets did not differ significantly in the light to moderate smokers compared with non-smokers, in vitro T-suppressor function against the Ig-secreting response of allogeneic B-cells to pokeweed mitogen (PWM) stimulation was significantly impaired. The proliferative response of T-cells to phytohaemagglutinin (PHA) was, however, similar in both groups. This suggests that smoking may exert a selective influence upon a subset of T suppressor cells. In cytotoxicity assays, smokers showed a significant decrease in natural killer cell (NK) activity but not in antibody dependent cellular cytotoxicity (ADCC). It appears that these alterations are reversible since a group of ex-smokers (n = 10) were indistinguishable from our non-smoking group in all studies. The implications regarding the link between smoking and increased susceptibility to infection and malignancy are discussed; and these findings should be borne in mind in basic studies of lymphocytes.

Adult↗
PubMed1984

Clinical significance of circulating immune complexes in 'lone' cryptogenic fibrosing alveolitis and those with associated connective tissue disorders.

The clinical, radiographic and physiological features, and progression rates of forty unselected patients with cryptogenic fibrosing alveolitis (CFA) have been studied in relation to serum immune complexes measured by a C1q binding technique. Twenty (50%) had levels greater than normal. Those with associated connective tissue disorders (twenty-four) had a higher frequency of raised C1q binding than those with 'lone' CFA (sixteen) (63% compared to 31%). As observed previously in this group, those with associated disorders also had higher titres of immune complexes. Twelve of thirteen with polyarthritis had immune complexes and a considerably shorter duration of disease compared with those without joint symptoms (P less than 0.01). Several other observations suggest that immune complexes are especially associated with earlier disease. These include a trend towards a younger age and a lesser radiographic profusion score; a shorter duration of symptoms in relation to titres of immune complexes amongst those with raised values (P less than 0.05) and a higher transfer factor coefficient (Kco) (P less than 0.02). The relationship between Kco and the presence of immune complexes was still observed when those with 'lone' CFA were analysed separately. Other clinical features including sex, severity of dyspnoea and lung volumes did not distinguish those with and without complexes, either for the whole group of patients or when those with and without associated connective tissue disorders were analysed separately. Analysis of eighteen patients followed to death showed no correlation between length of survival from first symptoms and immune complexes, neither was there any clear association with corticosteroid responsiveness and immune complexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-Antibody Complex↗
PubMed1984

Serum type III procollagen peptide concentration in cryptogenic fibrosing alveolitis and its clinical relevance.

The serum concentrations of a metabolite produced during synthesis type III collagen, type III procollagen peptide (PCP), were measured in patients with cryptogenic fibrosing alveolitis, and the results were related to the course of the disease and its response to treatment. The mean PCP concentration was significantly higher for patients untreated at the time of sampling than for an age and sex matched control group (p less than 0.001). Seventeen of these patients subsequently started treatment and their response to treatment was assessed by measurement of changes in the transfer coefficient (KCO) and forced vital capacity (FVC) at six months and one year later. Those patients showing a response to treatment, indicated by an increase in the percentage predicted KCO or FVC of more than 10% one year after starting treatment, had a significantly higher mean PCP concentration (p less than 0.01 and p less than 0.001 respectively) than patients with stable or deteriorating physiological indices. When the PCP concentrations of these patients were compared with repeat measurements three to six months after the commencement of treatment 14 out of 17 showed a decrease in PCP levels. This percentage change in PCP concentrations correlated significantly with the change in the percentage predicted KCO and FVC at 12 months after the commencement of treatment (p less than 0.01). These results suggest that measurement of PCP concentrations in patients with cryptogenic fibrosing alveolitis may be useful in the assessment of response to treatment.

Adrenal Cortex Hormones↗
PubMed1984

Definition and clinical relevance of antibodies to nuclear ribonucleoprotein and other nuclear antigens in patients with cryptogenic fibrosing alveolitis.

Antinuclear antibodies (ANA) were studied in 122 patients with cryptogenic fibrosing alveolitis (CFA) and compared with age- and sex-matched control subjects. Fluorescent ANA were detected in 32% of the patients and showed a correlation with the presence of a systemic connective tissue disease; ANA were present in 6% of the control subjects, 21% of the patients with CFA alone, and 46% of those with CFA and an associated connective tissue disease. Antibodies to the defined nuclear antigens: deoxyribonucleic acid (DNA), nuclear ribonucleoprotein (nRNP), the Sm antigen, and Sjögren's syndrome A and B antigens (SS-A and SS-B) were examined to establish whether their presence was diagnostic of the associated diseases. Antibodies to DNA and Sm antigens identified 3 patients with CFA and systemic lupus erythematosus. The frequency of antibodies to SS-A and SS-B did not differ from that in control subjects. Antibodies to nRNP, detected in 15 (12%) of the patients (at a high titer in 5), were associated with females, the presence of Raynaud's phenomenon, and rheumatoid factor in the serum. However, despite the detection of these antibodies, none of these patients met fully the proposed criteria for the diagnosis of mixed connective tissue disease.

Adult↗
PubMed1984

Digital vasculitis in patients with cryptogenic fibrosing alveolitis.

Twelve patients are described with features of cryptogenic fibrosing alveolitis (CFA) with associated florid digital vasculitis (DV). Nine patients had features of various 'connective tissue disorders' involving systems other than the lung, but three had no such features. The immunological features of these patients with DV have been compared with a group of 17 patients who had CFA alone ('lone CFA') and in whom the same range of special laboratory tests were being undertaken concurrently. The group with DV had a higher erythrocyte sedimentation rate and a higher serum IgM, but the most interesting immunological distinction was an increased prevalence of antinuclear antibodies with a nucleolar staining pattern. In addition, the group with DV also had a greater prevalence of single stranded DNA antibodies and of smooth muscle autoantibodies. Circulating immune complexes were not detected more frequently in the group with vasculitis. Ten of the 12 patients were initially treated with corticosteroids and neither the vasculitis nor the lungs improved. In eight the incapacitating DV responded to immunosuppressants (four) or penicillamine (four). In three of these eight patients the lungs also improved.

Adult↗
PubMed1983

Interstitial lung disease and asthma in hard-metal workers: bronchoalveolar lavage, ultrastructural, and analytical findings and results of bronchial provocation tests.

Five patients with respiratory disorders associated with hard metal exposure are described. In four patients electron microprobe analysis of bronchoalveolar lavage cells or lung tissue was used to show tungsten and other hard-metal components. Three patients had interstitial pneumonia and fibrosis with unusual multinucleate giant cells. Electron microscopy showed that the giant cells comprised both type II alveolar epithelial cells and alveolar macrophages. The multinucleate macrophages formed a distinctive feature of the bronchoalveolar lavage material but the multinucleate alveolar epithelial lining cells were evident only in lung tissue. The other two patients both suffered from work-related asthma, one of whom also had pulmonary opacities. Bronchial provocation tests in these patients supported the diagnosis of hard-metal-induced asthma and implicated cobalt as the agent responsible.

Adult↗