PubMed Health⌕ Search

Biomedical subjects

M A Spiteri

Publications and source records attributed to M A Spiteri.

At least 19 recordsLinked to original sources
PubMed1992

Seasonal cryptogenic organising pneumonia with biochemical cholestasis: a new clinical entity.

The term cryptogenic organising pneumonia has been used for the combination of dyspnoea, cough, pleuritic pain, widespread shadows on chest radiographs, and histological evidence of intra-alveolar organisation with buds of granulation tissue within the alveoli. We report 12 patients with seasonal recurrence of this disorder for between 3 and 11 years. In all 12 patients, symptoms recurred between late February and early May every year, tending to increase in severity each year, and resolved between June and January. Chest radiography and computed tomography showed bilateral consolidation. Lung biopsy samples showed intra-alveolar buds of granulation tissue. There were many neutrophils within the lumina of medium-sized airways and terminal bronchioles showed evidence of obstruction by granulation tissue. Functionally, the predominant defect was restrictive and only 2 patients (life-long non-smokers) had airflow limitation. All 12 patients had very high activities of liver enzymes, suggesting intrahepatic cholestasis, but no other evidence of liver disease. Cultures of blood, sputum, lung tissue, and bronchoalveolar lavage fluid, viral screening, and complement fixation tests were consistently negative. In all patients all abnormalities responded rapidly to oral steroid therapy. These findings suggest a seasonal syndrome of organising pneumonia and biochemical abnormalities indicative of intrahepatic cholestasis. No aetiological factor has been identified, but the nature and periodicity of the illness point to an inhaled agent present in the environment for a limited period every year.

Adult↗
PubMed1992

Effect of temazepam on tracheobronchial mucus clearance.

BACKGROUND: Tracheobronchial clearance of mucus from the lungs is reduced during sleep and, usually, by the administration of opiates. It seemed possible therefore that temazepam, a widely used potent benzodiazepine, retarded clearance. METHODS: The effect of 10 mg temazepam on mucociliary clearance was studied in eight healthy volunteers, aged 18-50 (mean 30) years, in a randomised, placebo controlled, double blind, cross-over study. Six subjects were female and two male. Six were non-smokers and two were light current smokers. Clearance was assessed from the change in radio-activity in the lungs after inhalation of 5 microns diameter polystyrene particles, labelled with technetium-99m, under controlled conditions. RESULTS: Tracheobronchial clearance was reduced by 22% after temazepam by comparison with placebo during the first three hours after drug ingestion; this is the period when circulating drug concentrations are highest. CONCLUSION: Temazepam should be prescribed with caution in patients with impaired lung mucociliary transport.

Adolescent↗
PubMed1992

Alveolar macrophages that suppress T-cell responses may be crucial to the pathogenetic outcome of pulmonary sarcoidosis.

The alveolar macrophage (AM) population is widely recognized to be heterogeneous; distinct subpopulations can be identified by the use of macrophage-specific monoclonal antibody (MoAb) probes. We have isolated a macrophage subset that appears to react with both MoAbs that have previously discriminated between dendritic cells and classic macrophages. In the bronchoalveolar lavage (BAL) of patients with active sarcoidosis the proportion of this specific AM subpopulation increases dramatically (30.4 +/- 4.01% compared to 6.14 +/- 1.56% in normal BAL). This AM subset not only increases in direct proportion to the lavage lymphocytosis, but also exhibits sarcoid-related differences in surface receptor expression, physiology and induction of T-cell responses. An increased number of these AM expressed a separate antigen RFD9 (which identified epithelioid cells), and had raised fibronectin content, increased phagocytosis, and high lysosomal enzyme activity. Of functional significance, we found that while in normal volunteers this specific AM subset was capable of down-regulating by as much as 40% the induction of T-cell responses set up by other stimulator macrophages, in sarcoid patients this suppressor activity was enhanced, such that T-cell responses were completely abolished. In some studies this action was masked by the reduced enhancing capacity of sarcoid inducer AM. We postulate that the presence of an increased proportion of these suppressor AM (together with their sarcoid-specific features) in active sarcoidosis is of crucial significance in determining the fate of granulomata in the lungs of these patients.

Adult↗
PubMed1992

Isolation of phenotypically and functionally distinct macrophage subpopulations from human bronchoalveolar lavage.

Bronchoalveolar lavage was used to obtain alveolar macrophages (AM) from the lower respiratory tract of healthy normal volunteers. Monoclonal antibody (MoAb) probes specific against macrophage determinants were then applied, in conjunction with density separation techniques, to identify and isolate three relatively homogeneous subpopulations from the AM pool. The MoAbs used, RFD1 and RFD7, have previously been shown to differentiate between "dendritic" cells and mature macrophages, respectively, in normal tissue. In addition to these two phenotypically distinct AM subsets (RFD1+D7- and RFD1-D7+ AM), a third AM subpopulation was isolated, which appeared to express both markers (RFD1+D7+). All three separated macrophage subsets were morphologically similar but exhibited distinct differences in surface receptor expression, enzyme content and physiology. Isolated RFD1+D7- AM (the phenotype of "dendritic" cells) did not adhere to the glass, had weak expression of C3b and FcR1 receptors, low fibronectin content and lysosomal activity; only a small proportion of these cells exhibited phagocytosis. The other two isolated AM subsets adhered to glass, expressed C3b and FcR1 receptors, had high fibronectin and acid phosphatase content, and a large majority exhibited phagocytic capacity; qualitative and quantitative differences in these features existed between the two AM subtypes. Furthermore, a diverse spectrum of hexose monophosphate shunt activity was observed throughout all three AM subpopulations, with the highest activity being recorded in the non-adherent AM. These data support the concept of a dynamic heterogeneity within the AM population. The variation in surface antigen expression and physiological capabilities observed amongst the three isolated AM subsets implies the presence of functionally distinct AM within the human lung, which, during steady-state conditions, may be critically balanced under the influence of stimuli in their local microenvironment. In support, proportional and functional shifts have been witnessed amongst these three AM subpopulations with the advent of disease.

Adult↗
PubMed1991

Characterization of immune inducer and suppressor macrophages from the normal human lung.

Monoclonal antibodies (MoAbs) that are able to discriminate between dendritic cells (MoAb RFD1+) and mature macrophages (MoAb RFD7+) in normal tissues were used in combination with density separation techniques to isolate relatively homogeneous subpopulations of macrophages from human bronchoalveolar lavage (BAL). A characterization of surface antigen expression, and functional capacity was then carried out on each isolated alveolar macrophage (AM) subset. One population with the phenotype RFD1+RFD7- obtained from the non-adherent cell pool showed the characteristics of antigen-presenting cells having absent or poor expression of Fc and C3b receptors, a low content of lysozomal hydrolase and poor phagocytic capacity. This population strongly stimulated T lymphocytes in allogeneic mixed lymphocyte reactions (MLR). A second AM population, isolated by adherence and density centrifugation expressed the phenotype RFD1+RFD7+. These cells showed the same phenotypic characteristics of mature macrophages with strong expression of C3b and Fc receptors, and marked phagocytic capacity. Such AM were very poor stimulators of allogeneic MLR. Under certain circumstances the RFD1+RFD7+ cells were shown to actively repress the stimulatory capacity of the RFD1+RFD7- subpopulation. These results suggest that variations within the functional capacity of AM subsets may be capable of influencing the strength of acquired T cell immune responses of the lung.

Acid Phosphatase↗
PubMed1990

Immunological features of lung lavage cells from patients with primary biliary cirrhosis may reflect those seen in pulmonary sarcoidosis.

To investigate the basis of subclinical alveolitis in patients with primary biliary cirrhosis, 10 primary biliary cirrhosis patients were studied by bronchoalveolar lavage. Both bronchoalveolar lavage lymphoid and non-lymphoid cell populations were analysed using immunocytological methods to determine their proportions and phenotypic features in an attempt to gain information as to possible immune mechanisms active in the lung of these patients. Six of the 10 patients in our study showed evidence of an alveolitis (raised lymphocyte count: 27.6 (4.3)% of total count) on lavage. The results were compared with control groups of normal volunteers and patients with active pulmonary sarcoidosis. The six primary biliary cirrhosis patients with lymphocytosis had a raised CD4/CD8 T-cell ratio (4.13:1), similar to the sarcoid patients (5.60:1). A proportion of these T-lymphocytes expressed markers of activation (HLA-DR+ 7.5 (2.1)%); CD25 + 2.3 (0.9)%; CD7 + 5.8 (1.5)%. This increased T-cell activation was also seen in the sarcoid groups (HLA-DR+ 10.0 (1.9)%; CD25 + 3.0 (1.1)%; CD7 + 5.0 (0.2)%). This was not seen in the primary biliary cirrhosis patients without lymphocytosis and the normal volunteers. Within the non-lymphoid cell population, an increase in dendritic (RFD1+) cells was seen in primary biliary cirrhosis patients with lymphocytosis (31.2 (1.9)%) and sarcoid patients (46.3 (5.1)%) in contrast with the normal and primary biliary cirrhosis group without lymphocytosis. The primary biliary cirrhosis patients without lymphocytes had a relatively greater proportion of mature phagocytes (RFD7+). We postulate that these observations suggest the emergence in the lung of a granuloma producing mechanism similar to that occurring in the liver. By comparison, the alveolitis found in primary biliary cirrhosis is consistent with that observed in interstitial granulomatous lung disorders such as sarcoidosis.

Bronchoalveolar Lavage Fluid↗
PubMed1989

Inhaled corticosteroids can modulate the immunopathogenesis of pulmonary sarcoidosis.

We investigated the effect of inhaled corticosteroids on the phenotypes and functional capacity of macrophages obtained by bronchoalveolar lavage from patients with pulmonary sarcoidosis. The results were correlated with clinical status and therapeutic efficacy. Ten symptomatic sarcoid patients (previously untreated) with radiological parenchymal shadowing and abnormal pulmonary function received inhaled budesonide, 800 micrograms m twice daily via a Nebuhaler for 16 weeks. A placebo group included ten healthy volunteers and five sarcoid patients with similar features to the treated group. Drug distribution studies showed that 10% of the inhaled drug was deposited in the alveolar region. All ten treated sarcoid patients had symptomatic relief with no adverse effects. Three of these ten patients had significant resolution of their radiological shadowing. No significant difference in pulmonary function was observed. At the cellular level, a significant decrease in lavage lymphocytosis was seen after 16 weeks, during which time there was a concomitant change in the phenotype and functional characteristics of the alveolar macrophage population. No similar changes were observed in the placebo group. Our results suggest that inhaled budesonide can modulate the aberrant immunological reactions existent in the lung in pulmonary sarcoidosis, and produce concomitant symptomatic relief with no side effects. It is postulated that this effect may occur through action on the local alveolar macrophage population.

Administration, Inhalation↗
PubMed1989

The macrophage in sarcoid granuloma formation.

Sarcoid granulomata result from aberrant immunological reactions initiated by antigen--presenting macrophage--like cells, and maintained by other effector macrophages. These macrophages can be distinguished phenotypically by monoclonal antibodies RFD1 and RFD7 (which recognize dendritic cells and mature macrophages respectively). Active sarcoid BAL contains a high proportion of RFD1 + cells (mean 44.7% compared to 12% in normals). Much of this increase is accounted for by the emergence of macrophages with the double phenotype RFD1 + D7 + (27.2% compared to 7% in normals), the proportion of which increases with disease severity and returns to normal in remission. When isolated from BAL by using plastic plate adherence and metrizamide density gradient, this hitherto unknown RFD1 + D7 + subset displays distinctive phenotypic, physiological and functional features. Unlike RFD1 + D7-cells, RFD1 + D7 + macrophages adhere to plastic, are acid phosphatase positive with increased phagocytosis, have marked Fc and c3b receptor expression, and suppress T-lymphocyte reactivity. In active sarcoidosis, this suppressive action is accentuated, and a greater proportion of RFD1 + D7 + cells express Fc receptors as well as a separate antigen RFD9 (which identifies epithelioid cells). Furthermore we have observed that gamma-interferon, produced in high concentration by activated T-lymphocytes induces not only HLA-DR molecules on cells, but has also been shown in vitro to increase the proportion of RFD1 + cells developing while suppressing RFD7 expression. It therefore seems that the increased proportion of RFD1 + D7 + macrophages seen in active sarcoidosis could arise as a result of an increased induction of RFD1 expression on macrophages which express RFD7.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1989

The nature of latent pulmonary involvement in primary biliary cirrhosis.

Primary biliary cirrhosis is a disease of unknown aetiology, resulting in progressive granulomatous destruction of small intrahepatic bile ducts. The rate at which this occurs varies considerably producing a wide clinical spectrum of the disease itself, as well as expression in other organs. Pulmonary manifestations in PBC have only been intermittently reported. Nevertheless in practice, a vast array of pathophysiological mechanisms can be implicated for the pulmonary dysfunction seen in some of these patients. The observed clinical features can be attributed to pulmonary vascular abnormalities, to a secondary 'fibrosing alveolitis', or indeed to the emergence of a granulomatous disorder in the lungs similar to sarcoidosis. Physicians should thus be aware of such potential lung complications, which can occur not only during the course of the PBC but also following liver transplantation.

Humans↗
PubMed1988

Reliability of eliciting physical signs in examination of the chest.

Agreement between 24 physicians on the presence or absence of respiratory signs was investigated. The physicians were divided into six sets of 4; each set examined 4 patients with well-defined chest signs. There was generally poor agreement about particular signs. Overall, the 4 physicians in a set were in complete agreement only 55% of the time. Some signs such as wheezing seemed to be more reliably elicited than others such as whispering pectoriloquy. Comparison of diagnoses based on the clinical findings with the correct diagnoses supported by investigations showed that 28% of physicians' diagnoses were incorrect. The more often the examiners differed from the majority on the presence or absence of a sign, the more likely they were to make an incorrect diagnosis. A ranked order of the reliability with which chest signs are elicited would improve the teaching of chest medicine.

Clinical Competence↗
PubMed1988

Subcutaneous adrenaline versus terbutaline in the treatment of acute severe asthma.

Subcutaneous adrenaline and terbutaline have been compared in a double blind study of 20 patients with acute severe asthma presenting to an accident and emergency department. Ten patients received adrenaline 0.5 mg (0.5 ml) and 10 terbutaline 0.5 mg (0.5 ml) subcutaneously. Further treatment with nebulised salbutamol (5 mg), hydrocortisone (200 mg), and aminophylline (0.9 mg/kg/hour) was started 15 minutes later. All patients reported a reduction in chest tightness within three minutes of receiving both adrenaline and terbutaline and reported no adverse effects. Mean baseline values of peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) did not differ significantly between the adrenaline group (130 1 min-1 and 0.83 l) and the terbutaline group (111 1 min-1 and 0.63 l). After administration of adrenaline PEF had increased by 21% and FEV1 by 40% five minutes after the injection, and by 35% and 64% at 15 minutes. Terbutaline caused a 23% increase in PEF and a 37% increase in FEV1 at five minutes, and a 40% and 58% increase at 15 minutes. There was no significant difference in PEF, FEV1, heart rate, blood pressure, or pulsus paradoxus between the two groups at any time. Continuous electrocardiographic recording showed no abnormalities in either group. Thus in this study subcutaneous adrenaline (0.5 mg) and terbutaline (0.5 mg) produced effective rapid bronchodilatation without serious side effects.

Acute Disease↗
PubMed1988

Apparent pulmonary mycetoma following invasive aspergillosis in neutropenic patients.

After the death from massive haemoptysis of two neutropenic patients who had developed apparent pulmonary mycetomas, two subsequent patients underwent successful resection of similar lesions. Histological examination of these lesions confirmed that these so called mycetomas were masses of devitalized lung tissue infiltrated with fungus. The term mycotic lung sequestrum is therefore proposed to distinguish this condition from a fungus ball arising in a previously formed cavity. A review of 34 similar cases reported previously showed that haemoptysis occurred in about half of the cases and was fatal in just over half of these. Medical treatment appears to have little impact on survival and early consideration of surgical intervention is important.

Adolescent↗
PubMed1988

Phenotypic and functional changes in alveolar macrophages contribute to the pathogenesis of pulmonary sarcoidosis.

Bronchoalveolar lavage (BAL) was performed on 10 patients with sarcoidosis and 10 normal volunteers. In each case aliquots of the lavage were used to prepare cytospins on which differential cell counts were performed. Immunocytological methods using monoclonal antibodies RFD1 and RFD7 (identifying dendritic cells and mature macrophages in normal tissues) were performed to identify macrophage subsets. Sarcoid BAL contained a significantly higher proportion of RFD1+ cells (mean 44.7 +/- 10.32% compared to 12.3 +/- 4.0% in normals). Much of this increase was accounted for by a highly significant rise in the proportion of cells with the double phenotype RFD1+/RFD7+ (27.2 +/- 6.1% in sarcoid compared to 7.3 +/- 2.0% in normal). Suspensions of sarcoid and normal BAL were also studied in autologous mixed lymphocyte reactions (AMLR) using peripheral blood mononuclear cells (PBM) as a responder population. AMLRs were therefore set up using BAL, PBM, and BAL with PBM. In each case reactivity was compared to mitomycin treated controls. These studies revealed that sarcoid PBM expressed markedly reduced AMLR reactivity when compared to normal but both sarcoid and normal BAL were relatively unreactive. BAL admixed with PBM suppressed peripheral blood AMLR reactivity in the normals. In sarcoid patients BAL admixed with PBM abolished AMLR completely. We suggest that changes within the BAL macrophage populations in sarcoid patients may significantly influence the pathogenesis of this disease.

Adult↗
PubMed1987

Necrotizing sarcoid granulomatosis.

We report a patient with necrotizing sarcoid granulomatosis (NSG) and point out that while the latter may have certain histological and radiological features distinct from sarcoidosis, sophisticated immunological tests show that the two disorders have essentially similar underlying immune mechanisms. We also stress that although the clinical course of NSG has been repeatedly described as benign and responsive to steroid therapy, the young patient may initially be critically ill with symptoms suggestive of an infective process rather than a granulomatous cause.

Adult↗