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Biomedical subjects

S G Spiro

Publications and source records attributed to S G Spiro.

At least 91 records · Page 5Linked to original sources

Pulmonary disease in Behçet's syndrome.

Five patients with Behçet's syndrome presenting with haemoptysis and recurrent radiographic opacities are reported, with a review of 23 similar cases. All 28 cases conformed to a definite clinical pattern with haemoptysis, usually accompanied by pyrexia, chest pain and dyspnoea, being the major feature. Typically pulmonary disease was associated with active disease at other sites, although the patients often only complained of haemoptysis. Patients with Behçet's syndrome and haemoptysis, compared to those without haemoptysis, showed a marked male predominance, with thrombophlebitis and deep vein thrombosis being more common. Rarely pulmonary disease occurred in the absence of one or other of the so called 'major' criteria on which the diagnosis of Behçet's syndrome is usually made, as was so for four of our patients who did not have ocular disease. Immunopathological evidence suggests that the underlying pathogenesis is a pulmonary vasculitis which may result in arterial and venous thromboses, pulmonary infarction, pulmonary haemorrhage and pulmonary arterial aneurysm formation. A role for immune complexes in the pathogenesis of pulmonary disease in Behçet's syndrome is suggested by the finding of circulating immune complexes in association with active pulmonary disease. Corticosteroids were initially helpful in treating active disease in the lungs, and at other sites, in most of the patients in whom they were tried, including our five patients, but serious haemoptysis occasionally recurred, despite further treatment. Four of our patients were initially treated with anticoagulants for a presumed diagnosis of pulmonary embolism, but continued to have haemoptysis. One of these patients subsequently died following massive haemoptysis, despite good anticoagulant control. The haemoptysis in most of the 28 cases was notable for its severity, and in at least 11 (39.3 per cent), pulmonary haemorrhage was the probable cause of death. All deaths due to haemoptysis occurred within six years of the first episode. Whilst pulmonary disease with haemoptysis is infrequent, it carries a very serious prognosis and for this reason correct diagnosis and appropriate treatment is imperative. Pulmonary disease with haemoptysis should be included as one of the so called 'minor' criteria in the diagnosis of Behçet's syndrome.

Adult↗

Radiation-induced lung fibrosis after treatment of small cell carcinoma of the lung with very high-dose cyclophosphamide.

Twenty-five previously untreated patients with small cell carcinoma of the lung were treated with cyclophosphamide 160 to 200 mg/kg (with autologous bone marrow support) followed by radiotherapy (4000 cGy) to the primary site and mediastinum. No other treatment was given until relapse occurred. Nineteen patients were assessable at least 4 months after radiotherapy; of these, 15 (79%) developed radiologic evidence of fibrosis, which was symptomatic in 14 (74%). The time of onset of fibrosis was related to the volume of lung irradiated. A retrospective analysis was made of 20 consecutive patients treated with multiple-drug chemotherapy and an identical radiotherapy regimen as part of a randomized trial. Radiologic and symptomatic fibrosis was one half as frequent (35%) as in the high-dose cyclophosphamide group. Very high-dose cyclophosphamide appears to sensitize the lung to radiotherapy and promotes the production of fibrosis.

Adult↗

Increased frequency of IgG heavy chain marker Glm(2) and of HLA-B8 in Lambert-Eaton myasthenic syndrome with and without associated lung carcinoma.

In view of the evidence for an autoimmune pathogenesis of the Lambert-Eaton myasthenic syndrome, we have sought associations with IgG heavy chain allotypes (Gm) and HLA antigens in 30 patients, of whom 20 had evidence of lung carcinoma (histologically proven small ("oat") cell type in 17). A highly significant overall increase in frequency of Glm(2) (chi 2 = 10.95; p less than 0.001; n = 30) and of HLA-B8 (chi 2 = 19.07; p less than 0.001; n = 23) was observed. These two factors apparently occurred independently of each other. The Glm(2) frequency in 36 non-myasthenic small cell carcinoma cases was the same as in a control panel (n = 167). We conclude that Glm(2) and HLA-B8 both associate with increased susceptibility to the Lambert-Eaton myasthenic syndrome, and suggest that Glm(2) may be in linkage disequilibrium with a limited number of VH genes coding for antibodies to restricted antigenic determinants at the nerve terminals, which may be shared by the carcinoma cells.

Adult↗

Social consequences of brain or liver relapse in small cell carcinoma of the bronchus.

The time spent in hospital when cerebral metastases occur as the first site of relapse in patients with small cell carcinoma of the lung (SCCL) has been analysed and compared to the consequences of relapse in the liver. In the course of a clinical trial with 370 patients, 50 patients relapsed initially in the brain and 20 in the liver. The 2 groups were comparable with respect to performance status at diagnosis and the amount of home support available. Patients who relapsed in the brain suffered a greater deterioration in performance status, and spent a greater proportion of their remaining life in hospital than did patients whose initial relapse was in the liver. This difference was most marked in patients who died soon after relapse. Radiotherapy (20 Gy in 5 fractions over one week or 30 Gy in 10 fractions over 2 weeks) and dexamethasone were not very effective treatments for brain relapse though subjective responses were common. The substantial morbidity and lengthy hospitalisation resulting from brain relapse compared with relapse at another site is a important factor to be considered in assessing whether prophylactic cranial irradiation should routinely be offered to patients with SCCL.

Adult↗

Neural markers in carcinoma of the lung.

Small cell carcinoma (SCC) is considered to be of neuroendocrine origin. Neurone specific enolase (NSE) and PGP 9.5 are markers of neural and neuroendocrine differentiation. S-100 protein is a marker of glial differentiation. The expression of these markers in endobronchial biopsy and lung tumour resection specimens was studied to see if any diagnostic, prognostic or therapeutic implications would emerge. Zamboni fixed endobronchial tumour biopsy specimens from 20 patients were examined. Twelve of these were cases of SCC and 8 were non-SCC. Of the 12 SCC, 7 were positive for NSE, 6 for PGP 9.5 and 5 for S-100 protein. Cases which showed a positive reaction for NSE had a mean survival of 9.1 months compared with 3.9 months for those with a negative reaction, but the number of cases is too small to assign any statistical significance. There was no difference in survival times between positive and negative reactors for PGP 9.5 and S-100 protein. All 8 cases of non-SCC showed positive reactions to all three markers. Of 32 formalin fixed lung tumour resection specimens 6 were cases of SCC, 25 non-SCC and 1 a chemodectoma. Three of the 6 cases of SCC showed positive staining for NSE, 3 for PGP 9.5 and 1 for S-100 protein. Of the 25 non-SCC, 10 were positive for NSE, 12 for PGP 9.5 and 6 for S-100 protein. The 1 chemodectoma stained positively for all three markers. Neuroendocrine markers are of little value in differentiating SCC from non-SCC. Positive staining for NSE in SCC may be an indicator of prolonged survival but further investigation is required.

Adenocarcinoma↗

High-dose cyclophosphamide in small-cell carcinoma of the lung.

Eighteen patients with untreated small-cell cancer of the lung have been treated with cyclophosphamide 200 mg/kg on two occasions at an interval of four weeks. An additional eight patients received etoposide in addition to cyclophosphamide. Measurements of tumor volume were made by thoracic computed tomographic (CT) scan before and after each cycle. When compared with our previous study in which only one cycle of cyclophosphamide was given, the double procedure did not increase response rate, decrease the incidence of local relapse, or prolong the relapse-free interval. Survival after relapse was shorter with two cycles of chemotherapy mainly due to greater difficulty in administering further chemotherapy. The CT scans showed a decrease in tumor volume from 99.2 cc to 21 cc after the first cycle, but a smaller decrease to 14.1 cc after the second. These results show that the rapid emergence of drug resistance imposes limitations on the use of very high-dose cytotoxic chemotherapy.

Adult↗

Prognostic significance of laboratory parameters measured at diagnosis in small cell carcinoma of the lung.

An analysis of prognostic factors in small cell lung cancer has been carried out using data from 371 patients treated with identical chemotherapy in the context of a large prospectively randomized clinical trial. Prognosis was shown to be strongly correlated with initial performance status, disease extent, and routine biochemical tests at the time of diagnosis. Plasma albumin, plasma sodium, alkaline phosphatase, and gamma-glutamyl transpeptidase were all predictive of survival. An initial hemoglobin of less than 11 g/dl was also predictive, but age, sex, and initial WBC count were not. A multiple regression analysis identified performance status, plasma alkaline phosphatase, plasma sodium, disease extent, and plasma albumin as contributing independently to survival. Using these parameters, three prognostic groupings could be defined. The combination of performance status and the biochemical values more closely predicted survival than categorization on the basis of disease extent defined by clinical, radiological, and scanning criteria. Response to chemotherapy was strongly correlated with these prognostic groupings. A much higher response rate occurred in patients in the best prognostic category in whom the tumor mass is assumed to be smaller. These results provide a simple basis for predicting prognosis in small cell lung cancer and indicate that the better prognosis in chemotherapy responders is not solely due to the treatment.

Alkaline Phosphatase↗

Radiotherapy in small cell cancer of the lung treated with combination chemotherapy: a controlled trial.

Three hundred and seventy one patients with extensive or limited small cell cancer of the lung took part in a randomised trial to evaluate irradiation of the primary tumour in patients treated with combination chemotherapy. They were randomly allocated to treatment either with chemotherapy alone (198) or with both chemotherapy and radiotherapy (173). All 371 initially received 12 weeks of chemotherapy after which they were categorised according to response. Only those with stable or responding disease continued with their allotted treatment. Thus 144 received chemotherapy alone and 135 received both chemotherapy and radiotherapy. The design of the study permitted analysis of the effect of radiotherapy according to initial extent of disease and quality of early response to chemotherapy. Radiotherapy (40 Gy (4000 rad), one fraction a day over 20 days) did not improve the survival of patients in any category of initial extent of disease or early response to chemotherapy and was not effective in preventing local relapse.

Carcinoma, Small Cell↗

Characterization of the late response in exercise-induced asthma.

Nine young adult subjects who developed asthma after a standard treadmill exercise test were studied. Pulmonary function tests were performed before and after exercise and serially for at least 6 hr afterwards. The subjects performed pulmonary function tests while breathing room air and after breathing an oxygen-helium mixture with each test. Although pulmonary function returned to normal within 3 hr after exercising in all subjects, eight of the nine had late asthmatic reactions 3 to 5 hr afterward. In general the late response was less severe than the initial response. Two subjects, however, noticed clinical asthma. In the immediate response, eight of the nine subjects were helium "responders," suggesting that the immediate response involved both large and small airways. In the late response, seven of eight subjects were helium "nonresponders," suggesting that the late response occurred primarily in small airways.

Adult↗

Direct labelling of ipratropium bromide aerosol and its deposition pattern in normal subjects and patients with chronic bronchitis.

A technique for the direct labelling of ipratropium bromide with bromine-77, with reconstitution of the drug in a metered dose inhaler so as to be identical to the commercial product, was used to study drug deposition patterns in seven normal subjects and seven patients with chronic bronchitis (mean FEV1 32% (SD 12.2%) predicted normal). The gamma camera image of the thorax was divided into a middle zone--the mediastinal zone--and the lung itself into a central zone comprising its medial third and a peripheal zone, the lateral two thirds. Measurements after 10 inhalations of labelled ipratropium bromide showed similar results for the two groups of subjects. The total lung dose inhaled was 11.2% of 203 micrograms and 11.7% of 186 micrograms in the normal subjects and the patients respectively. In contrast to the deposition patterns seen in aerosol studies using steady state inhalation methods, there was no difference in deposition pattern--that is, the distribution between the central and the peripheral lung zones--between the normal subjects and the patients with airways obstruction.

Adult↗

Predicted normal values for maximal respiratory pressures in caucasian adults and children.

Maximal respiratory pressures at the mouth (PEmax and PImax) have been measured in 370 normal caucasian children and adults. Age, height, and weight were recorded for all subjects and incorporated in a stepwise multiple regression analysis to determine prediction equations for the maximal respiratory pressures in the children and adults for both sexes. In men PImax and PEmax were significantly correlated only with age (p less than 0.001 and less than 0.035 respectively), whereas in women they were correlated with height (p less than 0.035 and less than 0.03). In both boys and girls PImax was related to weight (p less than 0.0001 and less than 0.01 respectively) and PEmax to age (p less than 0.001 for both). The values for PImax and PEmax in adults were lower than in previously reported series, but in children the values obtained were similar to those reported for several smaller series.

Adolescent↗

Sternomastoid muscle function and fatigue in normal subjects and in patients with chronic obstructive pulmonary disease.

Four normal subjects and 5 patients with chronic obstructive pulmonary disease (COPD) (mean FEV1, 1.03 L) had frequency:force curves of their sternomastoid muscle measured before and 5 min after a 12-min walk on a flat treadmill, a progressive exercise test (normal subjects only), and a 10-min period of sustained maximal voluntary ventilation (SMVV). Before each test, all subjects had a normal frequency:force curve, and the ratio of the force response at 20 Hz to that at 50 Hz was normal. After SMVV, all the normal subjects and 4 of the 5 patients developed a greater than 15% fall in 20:50 ratio, and this was taken to indicate the presence of low frequency fatigue (LFF). During SMVV, all the subjects achieved minute ventilation greater than 70% of predicted maximal breathing capacity (MBC). During the 12-min walk, all the patients exceeded 70% MBC, and 4 developed LFF. The normal subjects performing progressive exercise also exceeded 70% MBC, and all showed LFF. The 12-min walk did not cause LFF in the normal subjects, but no subject reached 70% of MBC. Despite the presence of LFF in the sternomastoid muscle, the patients were all able to walk the same distance during a second 12-min walk. In both the normal and patient groups, the ventilatory response to CO2 was not changed by the presence of LFF. There were no changes in maximal inspiratory and expiratory mouth pressures or spirometry with LFF. High, sustained levels of minute ventilation cause sternomastoid LFF, but the clinical significance of this phenomenon is not yet certain.

Adult↗

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↗