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Declan J Meagher was a most influential figure in Irish obstetrics and gynaecology during the 1960s, 70s, and 80s, making huge contributions to maternal and infant welfare. He was born in Ferbane, County Offaly, where his father, William Meagher, was the local doctor. This was a time of great turbulence in Ireland between the war of independence and the civil war. Declan was educated initially by the local Christian Brothers and subsequently the Jesuits in Clongowes Wood College in County Kildare. He studied at University College Dublin and graduated with distinction in 1944. He decided on a career in obstetrics and gynaecology and trained initially at the National Maternity Hospital and then at the Hammersmith Hospital in London. By this time he had married Emer McMullin. Later, he was to wryly recall their impecunious postwar London days, living in very spartan, cramped accommodation; meat was a rare treat. On his return to Dublin, now with a young family, he was appointed to the staff of the National Maternity Hospital, the hospital to which he was to devote his life’s work. In 1965 he joined the consultant staff …

A growing number of studies on the mechanism of leukocyte transendothelial migration use endothelial cells grown on microporous filters as an in vitro model of endothelium. Ultrastructural examination of such a model system previously demonstrated that human pulmonary artery endothelial cells (HPAEC) formed confluent monolayers on both sides of the 3-microm-pore filter (Mackarel et al., 1999). To determine whether this was a characteristic specific to pulmonary artery endothelial cells, the growth characteristics of a human pulmonary microvascular endothelial cell type (HMVEC-L) and the widely used human umbilical vein endothelial cells (HUVEC) on 3-microm microporous filters were examined by transmission electron microscopy (TEM). Similar to HPAEC, HMVEC-L and HUVEC were also found to grow on both sides of the filter. All three endothelial cell types were capable of migrating through the 3 microm pores of the filter to form a monolayer on the filter underside. The endothelial cells on the underside were orientated in an inverted position with the luminal surface facing away from the filter. Such 'bilayer' formation was observed at a range of seeding densities and in different culture media. Despite the presence of a bilayer of endothelial cells, TEM demonstrated that neutrophils migrated successfully across the cell-filter-cell system. Previous transmigration reports in which an in vitro model similar to ours was used have often assumed only one layer of endothelial cells. The observations reported here indicate that while endothelial cells on microporous filters are useful models for examining leukocyte-endothelial interactions, they are not appropriate for studies examining endothelial cell 'sidedness.'

Patients with cystic fibrosis (CF) have a high prevalence of Pseudomonas aeruginosa infection which causes chronic infection of the mucosal surfaces of the lung. This results in recurrent immune stimulation and hypergammaglobulinemia. The present study examines the levels of circulating Ig classes, IgG and IgA subclasses in 13 adult patients with CF during acute pulmonary infection and post-exacerbation. Total serum IgG levels were raised in the patients during infection and post-treatment when compared to the normal range (mean +/- SEM: 17.21 +/- 1.4 g/l vs 16.45 +/- 1.5 g/l respectively; normal range 8-16 g/l). In contrast, total IgM (2.6 +/- 0.26 vs 2.69 +/- 2.74 g/l; normal range 0.6-2.8 g/l) and IgA levels (2.5 +/- 0.52 vs 2.41 +/- 0.48 g/l; normal range 0.5-4 g/l) remained unchanged when examined during all stages of the disease. Of the 13 patients studied, 69%, 39% and 31% had IgG, IgM and IgA levels respectively raised above the normal range values. The mean levels of individual IgG subclasses examined in this group of patients revealed values within the normal ranges, however IgG2 and IgG3 were increased in 31% and 46% of patients. Individual IgG3 levels fell in 77% (10/13) and IgG4 in 62% (8/13) of the patients post-exacerbation. With regard to IgA subclasses, significant reduction in the IgA1 levels were observed post treatment (3687 +/- 539 mg/l vs 2713 +/- 498 mg/l, p0.01). In contrast, IgA2 levels were increased from 279 +/- 49 mg/l to 421 +/- 69 mg/l, although statistical significance was not reached. Upon antibiotic treatment for infection, the findings in this study show that IgA1 which is susceptible to bacterial proteases is reduced with a concommitant increase in the protease resistant IgA2 subclass. Moreover, patients colonised with non-mucoid strains of P. aeroginosa had higher total IgA levels due to the raised IgA1 subclass whereas they had lower IgG levels due to low IgG2 and IgG4 subclasses.

The Birmingham scoring system for chest radiographs was assessed in 40 adult cystic fibrosis patients, with particular reference to correlation with pulmonary function values. Forty 'initial' and forty 'follow-up' chest radiographs were scored. The mean initial age of the group was 17.5 +/- 5.0 years, and the mean age at follow-up was 23.3 +/- 5.3 years. The cross-sectional radiographic score correlated significantly with the values of three commonly measured, pulmonary function parameters (r = 0.65, 0.67, 0.58, P less than 0.0001). There was a significant correlation (r = 0.64, P less than 0.0001), between the change in radiographic score, and the change in percent predicted forced vital capacity (FVC%). There was a less significant correlation (r = 0.45, P less than 0.006) between the change in radiographic score and the change in per cent predicted forced expiratory volume in one second (FEV1%). We conclude that the Birmingham radiographic scoring system is suitable for quantitative radiological evaluation in adult cystic fibrosis.

The practical use of lactate electrochemical analysers in exercise testing has not been adequately examined. Initial studies have reported differences in lactate concentration between that measured spectrophotometrically and that measured electrochemically. The study described here was undertaken to compare, using the statistical technique of Bland and Altman (1986), two widely available methods of measuring lactate using lysed and non-lysed blood samples and the lactate thresholds derived from the measured lactate values using a log-log transform technique. Thirteen normal, healthy young adults (11 male) undertook progressive exercise tests to exhaustion. Arterialised venous blood samples were taken each minute and the lactate concentration therein was measured both spectrophotometrically and electrochemically and either with or without lysis of the blood samples. The lactate concentrations measured in lysed blood using both methods (182 pairs) were in close agreement. The electrochemical values obtained using non-lysed blood were systematically lower than spectrophotometric values (206 pairs), the difference becoming progressively greater at higher lactate concentrations. Results for the lactate threshold comparisons are given as mean difference (limits of agreement with 95% probability). Lactate thresholds (12 pairs) derived from lysed blood lactate concentrations measured spectrophotometrically and electrochemically were not significantly different -30 (240) ml O2 x min(-1). Lactate thresholds (11 pairs) derived from lysed spectrophotometric and non-lysed electrochemical measurements were also not significantly different + 20 (250) ml O2 x min(-1). Thus, despite the difference in the measured lactate concentrations, the derived lactate thresholds are in agreement and, therefore, electrochemical analysers can be used for lactate threshold determination using the log-log transform technique without sample lysis.

Reactive Airways Dysfunction Syndrome (RADS) has been described following exposure to various irritant gases(1). We describe a case of RADS occurring following exposure to chlorine gas and which has persisted at 6 years follow-up.

To assess the correlation between HRCT and pulmonary function in patients with CF. Further, to assess the prognostic value of HRCT in these patients.Clinical examination, chest radiographs and HRCT scans on 30 CF patients with an average age of 17 were scored using established scoring systems. The results were correlated with FEV1 and FVC both at time of CT scanning and after 30 months. Results were also correlated with the clinical progress of the patients over the follow-up period.HRCT, chest radiograph and clinical examination demonstrated similar correlation (p0.001) with FEV1 and FVC at the time of scanning. HRCT demonstrated the closest correlation with the clinical progress of the patients over the follow-up period and with follow-up pulmonary function. A maximum combined score for bronchiectasis and emphysema on HRCT seemed to indicate a poor prognosis.HRCT in CF patients correlates well with pulmonary function at time of scanning and at follow-up, and with clinical progress. There may be a role for CT in the identification of adolescent/adult patients who can be expected to need aggressive therapy in the future.

The improved survival of cystic fibrosis (CF) patients is partly due to intensive treatment for their chronic infections. Treatment usually includes intravenous and nebulised aminoglycoside antibiotics and they receive a large cumulative dose of these antibiotics over their lifetime. There is little information in the literature on the prevalence of ototoxicity due to aminoglycoside in these patients. We performed pure tone audiometry on 43 CF patients aged 14-42 years. Seven (16%) had bilateral sensorineural hearing loss (SNHL) for high frequency sounds, consistent with aminoglycoside induced ototoxicity. However, only 2 of these patients had documented toxic serum levels in the past. The identification of bilateral SNHL in one in six adult CF patients is a cause for concern. It may be that the high cumulative dose of aminoglycosides received by these patients may be causing inner ear injury in the absence of specific episodes of toxic serum levels.

In cystic fibrosis, a majority of patients develop persistent lifelong respiratory tract colonisation with pseudomonas aeruginosa while a minority do not appear to become colonised. There is some evidence that non-secretion of ABO Blood Group antigens into body secretions is a marker for susceptibility to certain gram negative infections. Therefore, we studied 47 adult patients with cystic fibrosis to identify an association, if any, between secretor status and the presence or absence of pseudomonas aeruginosa in their sputum. Overall, we found no difference between the prevalence of non-secretors in our patient group and in the normal population. Furthermore, there was no association between secretor status and presence or absence of pseudomonas aeruginosa in sputum. We conclude that secretor status is unlikely to play a major role in susceptibility to pseudomonas aeruginosa infection in patients with cystic fibrosis.

We report a case of intravenous talcosis in a 36 year old woman. Although she initially denied drug abuse clinical suspicion was aroused by the finding of obliterated peripheral veins, a pleural rub and a peripheral nodular lesion on chest x-ray. Diagnosis of intravenous talcosis was confirmed by finding birefringent particles on transbronchial biopsy. Confronted with this evidence the patient admitted long-standing drug abuse, including intravenous injection of crushed methadone tablets which contain talc filler.

The prevalence of peripheral nerve dysfunction was assessed in 24 randomly selected adult patients with cystic fibrosis. Median, peroneal and sural nerves were studied. In 15 patients (62%), one or more electrical abnormality were detected. In the median nerve, conduction velocity was slowed in 29% of sensory studies and 12.5% of motor studies; compound muscle action potential (CMAP) and sensory nerve action potential (SNAP) amplitudes were normal. The CAMP was low in 17% of peroneal studies with motor conduction velocity slow in 8%. The sural SNAP was low in 17% and sensory nerve conduction velocity slow in 25%. Using a multiple regression analysis only age at diagnosis was identified as a significant predictor of peripheral nerve dysfunction (multiple R = 0.55; p < 0.01). This study demonstrates that mild peripheral nerve dysfunction is common in patients with cystic fibrosis. With the improving long term survival of these patients we predict that the prevalence and severity of this complication will increase.

THIS paper is a retrospective study of thirty-nine patients with lung disease, caused by aspergillus fumigatus, seen in two large general hospitals over a ten year period. The study was undertaken to establish the pattern and distribution of pulmonary aspergillosis in this group with particular emphasis on the nature of the underlying disorder, management and outcome. The patients fell into three well-defined categories: 1. Localized aspergilloma (fungus ball, mycetoma)-20 patients. 2. Allergic bronchopulmonary aspergillosis (ABPA)-12 patients. 3. Invasive aspergillosis — 7 patients. The aspergilloma group was characterized by severe, preexisting lung disease, poor pulmonary function and, in 50% of cases, life-threatening heamoptysis. This complication was treated surgically (5 cases), by embolisation of the bronchial artery (3 cases) or conservatively (2 cases) depending on clinical and physiologic status. In the ABPA group, all patients had asthma. Seven patients (58%) had bronchographically proven bronchiectasis at the time of diagnosis of ABPA and all but one required long-term oral steroid therapy. The 7 cases of invasive aspergillosis comprised 5 patients with underlying neoplasm, one with myelofibrosis and one with systemic lupus erythematosis most of whom were on some form of immunosuppressive therapy. Surprisingly, clinical and radiologic findings were subtle. In 4 of these 7 cases (57%), aspergillosis precipitated the terminal event and in five of these cases (71%), the diagnosis was not made until post-mortem examination. These data emphasise the diverse mechanisms by which aspergillus fumigatus can cause serious pulmonary pathology. Despite the wide differences in etiopathogenic mechanisms of the three groups, a striking common denominator in this group was the advanced stage of the disease at the time of diagnosis. There is a need for heightened awareness of the importance of aspergillus fumigatus as a complication of fibrotic lung disease, of ABPA in asthma and of invasive aspergillosis in neoplasm and disease associated with immunosuppression.

In 1972, to study slight manifestations of pulmonary fibrosis due to asbestos, we evaluated 101 shipyard pipe coverers and 95 control subjects whom we had examined in 1965 and in 1966. Although these workers had been exposed to low levels of asbestos, "asbestosis" was diagnosed in the first survey 11 times more often among pipe coverers than among control subjects. In 1972, clinical, roentgenologic and physiologic tests for monitoring workers were evaluated with respect to (1) ability to separate pipe coverers from control subjects, (2) consistency from the initial to the final survey, (3) predictive value in 1966 with respect to health in 1972 and (4) relationship to duration of exposure. Basilar rales, irregular opacities on chest film, and reduced vital and diffusing capacity were more common in pipe coverers in both surveys. These findings tended to be abnormal in 1972 in those workers in whom they were present in 1966, whereas dyspnea and clubbing were inconsistently found. The predictive value of a single abnormality was minimal, whereas the prognosis was poor in the nine pipe coverers who had three or more of these criteria in 1966. "Asbestosis" was considered present when three or more of the following were present: (1) bibasilar fine rales, (2) irregular x-ray opacifications (International Labour Organization, University of Cincinnati Classification [ILO/UC] 2/1 or more), (3) forced vital capacity (FVC) less than 80 per cent predicted, (4) single breath diffusing capacity (Dsb) less than 80 per cent predicted. There was only one false positive, a worker with significant heart disease. Clusters of findings appear more important for monitoring exposed workers than single findings. An incidence of 1.1 per cent/year of asbestosis, despite an 80 per cent reduction in the total quantity of asbestos used, emphasizes the importance of environment control.

Using ear oximetry, we studied the oxygen saturation in nine patients with cystic fibrosis who were undergoing chest physiotherapy. All nine subjects showed desaturation, seven to a level of less than 85%. Supplemental oxygen failed to prevent this but did promote a more rapid return to baseline. Chest physiotherapy is not without risk. Patients receiving such therapy require close observation and may benefit from supplemental oxygen.

We measured serum trypsin by radio-immunoassay and differential serum amylases using an inhibitor technique, in 24 patients with cystic fibrosis (C.F.), 20 of whom had symptomatic steatorrhea, and 24 normal controls. Both mean serum trypsin and pancreatic isoamylase were significontly lower in the 20 C.F. patients with symptomatic steatorrhea than in the controls (p

Patients with confirmed interstitial pneumonia were initially classified histologically into "desquamative" (n = 40) and "usual" (n = 53) types, and followed for one to 22 years. Both the diagnosis and the extent of fibrosis affected the course and response to therapy. Mortality in desquamative interstitial pneumonia was 27.5 per cent, and mean survival 12.2 years, as compared with 66.0 per cent and 5.6 years in usual interstitial pneumonia (P less than 0.01). Without treatment, 21.9 per cent with the desquamative but none with the usual type improved. With corticosteroid therapy, 61.5 per cent with desquamative and only 11.5 per cent with usual interstitial pneumonia improved, whereas 27.0 per cent and 69.2 per cent worsened. We conclude that the histologic classification of chronic interstitial pneumonia used here permits forecasts of prognosis and response to treatment that cannot be deduced from other data.

Gallium-67 (67Ga) lung scanning has been applied for some years in pulmonary sarcoidosis to assess the activity of the alveolitis. Interpreting the scans, however, is difficult due to the low uptake of 67Ga in the disease process relative to background activity. In this study we have measured the mean parenchymal lung activity of 67Ga and have compared the lung activity to that at three remote sites, the liver, the abdomen and the thigh. The results obtained were compared with the percentage of lymphocytes in broncho-alveolar lavage fluid. There was a very good correlation with the lung-to-thigh uptake measurements and a much poorer correlation with the lung-to-liver and the lung-to-abdomen measurements. It was observed that steroid therapy reduced dramatically the correlation between the broncho-alveolar lavage findings and the 67Ga scan measurements. The results suggest that in patients not on steroid therapy, the 67Ga lung-to-thigh measurements may be used, similarly to the broncho-alveolar lavage lymphocyte counts, to identify those with high-intensity alveolitis from those with low-intensity alveolitis.

The range and mean of serum IgG subclass levels in healthy adults (age range 20–60 years) are presented. While a wide range of individual sub-class levels is seen in the different age groups studied, all sub-classes remain at a constant level from 20–60 years of age. The availability of these results, using presently available reagents provides a baseline for further study on the role of IgG sub-class antibodies in health and disease.

Normal volunteers with previous marihuana smoking experience inhaled the total smoke from 3.23 mg per kilogram of marihuana, using a bag-in-box technic. Randomly, nine received marihuana containing a high (2.6 per cent), and eight a low (1.0 per cent) concentration of delta-9 tetrahydrocannabinol. Physiologic variables were monitored before and for 20 minutes after smoking. In the high-dose group the heart rate increased 28 per cent. Concomitantly, airway resistance, measured in a body plethysmograph, fell 38 per cent; the functional residual capacity remained unchanged (± 50 ml) throughout, and specific airway conductance increased 44 per cent. Flow-volume loops showed a 45 per cent increase in flow rate at 25 per cent of vital capacity. The low-dose group showed no increase in heart rate but significant, if lesser changes, in airways dynamics. Carbon dioxide sensitivity, measured by rebreathing remained unchanged in both groups. Marihuana smoke, unlike cigarette smoke, causes bronchodilatation ...

SUMMARY Five (8.5 per cent) of 59 adult patients with cystic fibrosis described a characteristic arthropathy which was episodis, self-limiting and polyarticular, affecting large and small peripheral joints without evidence of progression to joint damage. The five patients with arthropathy did not differ from the remaining 54 with respect to manifestations of cystic fibrosis. Synovial fluid obtained from two patients during acute episodes was clear, viscous and contained no cells. Biopsies of synovial membrance from the same patietns demonstrated prominent congested blood vessles with some synovial oedma, but no evidence of inflammation. Immunofluorescent staining of synovial membrance demonstrated characteristic ini\timal deposition of immunoglobulin in the vessles. In one of the two patients acute arthropathy was accompained by transient cutaneous vasculities, circulating immune complexes and lowered serum complement levels, which suggests that the episodic arthropathy in at least some patients with cystic fibrosis is mediated by an immune mechanism.

IN a review of eleven patients with aspergilloma attending St. Vincent’s Hospital between 1973 and 1984 sarcoid osis was the commonest predisposing disease (six patients) whereas cavitary tuberculosis, previously the most frequently associated condition, was present in only two patients. All patients had a combined restrictive-obstructive pulmonary deficit with mean values for FVC, FEV, and DLCO being 49%, 35% and 46% of predicted respectively. Life threatening haemoptysis was the most significant complication, occurring in six of eleven patients. In only two of these patients was lung function sufficiently adequate to permit surgical resection and both are alive 5 and 9 years respectively following the procedure. Four patients precluded from surgery because of prohibitive lung function had emergency bronchial arteriography performed with a vitw to arterial embolisation. This was successfully achieved in three patients with prompt cessation of active major haemoptysis, but could not be performed in a fourth because of an arterial anomaly. However there were no long term survivors in this latter non-surgical group. Finally, in five untreated patients observed over a mean period of three years, no major complications developed, despite enlargement of the fungus ball in three individuals. This study demonstrates a changing pattern of underlying disease in patients with aspergilloma and illutrates the usefulness of emergency arterial embolisation in the short term management of life threatening haemoptysis.

PANCREATIC disease is rarely reported in sarcoidosis. We describe 3 patients with sarcoidosis and acute pancreatitis. In a prospective study 15/92 patients with sarcoidosis had an abnormal level of serum pancreatic amylase and 6/39 had an elevated serum immunorective trypsin. These findings suggest that clinical and subclinical abnormalities of pancreatic function are not uncommon in patients with sarcoidosis.

2 observations rares: episodes de pancreatite aigue lies a la sarcoidose. Resultats favorables rapides du traitement par steroides, generalement contre-indique dans la forme courante de pancreatite

SummaryA 54-year-old man developed pigmentation, clubbing, weight loss, oedema, hepatomegaly, lymphadenopathy, cold intolerance, hypotonia and hyporeflexia. Dominant laboratory findings were increased marrow plasma cells with IgA lambda paraproteinaemia, hypothyroidism, hyperprolactinaemia, hyperoestrogenaemia and biopsy-proven peripheral neuropathy. The clinical features and dramatic response to corticosteroids are consistent with the syndrome of plasma cell dyscrasia, polyneuropathy and endocrinopathy found predominantly in Japan. In our patient, immunofluorescence of neural tissues revealed paraprotein deposition. Although the pathogenesis is unknown, these multisystemic features may result from antibody activity or tissue deposition of paraprotein. Furthermore, the endocrinopathy may be localized at the hypothalamic level.

Three cases of the rare disorder pulmonary alveolar proteinosis (PAP) presented to our unit over the past thirteen years. Two of the patients conformed to the classical description of idiopathic or "primary" PAP. One patient appeared to have co-existing extrinsic allergic alveolitis with "secondary" PAP, an association not previously described. This patient has required continued steroid therapy, a mode of treatment usually contraindicated in PAP.

Fibreoptic bronchoscopy has largely replaced rigid bronchoscopy in the intensive therapy unit. Retained bronchial secretions may be removed and difficult intubations performed with the flexible fibreoptic bronchoscope. In addition, it may provide uncontaminated lower airway samples for microbiological studies that can aid in the choice of antibiotic therapy. In our series of fibre-optic bronchoscopies performed on critically ill patients the procedure was effective in improving atelectasis in all cases in which retained bronchial secretions were found. In most patients the degree of bronchial occlusion by mucous plugs was far greater than expected on the basis of chest radiography. Fibreoptic bronchoscopy was also successful in diagnosing bronchogenic carcinoma, gastric content aspiration, bronchial avulsion and laryngeal oedema. We conclude that fibreoptic bronchoscopy is a safe and valuable procedure in the intensive care unit.

Portable electronic spirometers, often with direct readout, are now replacing conventional water or bellows spirometers for office, clinic and bedside use. Despite wide acceptance, perform...

Environmental lung diseases are reviewed with regard to classification, diagnosis, the chest roentgenogram, special diagnostic procedures, pathology, and evaluation of pulmonary impairment. Causes of environmental lung diseases are classified as follows: inorganic dusts containing free silica, silicates, carbon, and inert metals; biological dusts; toxic chemicals; microorganisms; and occupational respiratory carcinogens such as arsenic, cobalt, nickel, asbestos, and uraniund. The prevalence of bronchogenic carcinoma due to radioactive uranium among miners in Czechoslovakia is discussed and it is pointed out that there is an increased prevalence of carcinoma among uranium miners in Utah and Colorado. (HLW)

Sulphonamide antibiotics were once used in the 1940’s for their diuretic effects in heart failure. This property, long since forgotten, was responsible for a marked diuresis in a patient treated with co-trimoxazole, herein reported.

Rapid onset of severe and irreversible airflow obstruction developed in two women. One had eosinophilic fasciitis and the other had rheumatoid arthritis. Both were treated with penicillamine. In the first patient, aged 42 years, dyspnea developed after six months of therapy. Her roentgenogram showed hyperinflation. Forced vital capacity expired in one second (FEV1/FVC%) decreased from 75% to 40%, and the residual volume increased by 1 L. In the second patient, aged 54 years, cough and dyspnea developed after ten months of therapy. The FEV1/FVC% was 56%, the FEV1was 0.9 L, and the roentgenogram was normal. Lung biopsy specimens demonstrated severe and widespread bronchiolitis. An association between obliterative bronchiolitis and rheumatoid arthritis has been reported. Penicillamine may impair healing of bronchiolitis in such patients. (JAMA242:528-532, 1979)