The antibody response to methyl isocyanate: experimental and clinical findings.

As a result of the industrial accident in Bhopal, India (December 1984) in which thousands of people were exposed to methyl isocyanate (MIC), concern was raised for possible long-term health effects. The well-recognized immunologic consequences of exposure to other industrial isocyanates prompted investigation of an antibody response to MIC. Using procedures which had been developed in this laboratory to evaluate isocyanate immunotoxicity, animal studies were undertaken to develop and test reagents which could be used to detect antibodies to MIC in the exposed population. Guinea pigs were injected with MIC in its reactive isocyanate form. Three weeks later, blood was drawn and serum evaluated using ELISA. To detect antibodies, an antigen was prepared by reaction of MIC with guinea pig serum albumin. Antibodies were detected in each of the four animals injected with MIC. Titers achieved were 1:5120 to 1:10,240. Inhibition assays revealed antibody specificity directed toward the MIC hapten. Analogous antigens prepared by reaction of MIC with human serum albumin were used to evaluate sera from individuals exposed in Bhopal to MIC. Antibodies were detected in 12 of 144 exposed persons. Antibodies were specific for MIC, as evidenced by inhibition assays, and belonged to the IgG, IgM and IgE classes. However, titers were generally low and transient and were found in persons having had the highest MIC exposures. Total IgE values of sera were not significantly different from those of control sera obtained from Bombay residents. The results indicate that exposure to methyl isocyanate resulted in production of specific antibodies. However, the low titers observed and the transient nature of the response suggest little health consequence should result form the antibody response.

Sequential respiratory, psychologic, and immunologic studies in relation to methyl isocyanate exposure over two years with model development.

Of 113 methyl isocyanate (MIC)-exposed subjects studied initially at Bhopal, India, 79, 56, 68, and 87 were followed with clinical, lung function, radiographic, and immunologic tests at 3, 6, 12, 18, and 24 months. Though our cohort consisted of subjects at all ages showing a varied severity of initial illness, fewer females and young subjects were seen. Initially all had eye problems, but dominant symptoms were exertional dyspnea, cough, chest pain, sputum, and muscle weakness. A large number showed persistent depression mixed with anxiety, with disturbances of personality parameters. The early radiographic changes were lung edema, overinflation, enlarged heart, pleural scars, and consolidation. The persistent changes seen were interstitial deposits. Lung functions showed mainly restrictive changes with small airway obstruction; there was impairment of oxygen exchange. Oxygen exchange improved at 3-6 months, and spirometry improved at 12 months, only to decline later. The expiratory flow rates pertaining to large and medium airway function improved, but those for small airways remained low. There were changes of alveolitis in bronchoalveolar lavage fluid on fiber optic bronchoscopy, and in 11 cases positive MIC-specific antibodies to IgM, IgG, and IgE were demonstrated. On follow up, only 48% of the subjects were clinically stable, while 50% showed fluctuations. Thirty-two percent of the subjects had lung function fluctuations. Detailed sequential behavior over 2-4 years was predicted for dyspnea, forced vital capacity, maximum expiratory flow rate (0.25-0.75), peak expiratory flow rate, VO2, and depression score. A model for clinical behavior explained a total variance of 52.4% by using the factors of cough, PCO2 and X-ray zones in addition to above five parameters. The behavior of the railway colony group (1640 patients) revealed a similar pattern of illness. When this observed pattern of changes was transferred to the affected Bhopal city sections (with an equitable age-sex distribution), our model results were again validated. Thus the picture of MIC-induced disease seems similar despite the differences for age-sex and initial severity of illness in our cohort and in the population of Bhopal city as predicted by our model.

A study of lung function and oxygen uptake during exercises in cases undergoing mitral valve surgery.

In 1986-7, 80 cases with isolated mitral valve disease undergoing open heart surgery were studied, for spirometry, resting and exercise, oxygen uptake (VO2) preoperatively and 3 months postoperatively. Pulmonary artery pressures (PAP) were recorded prior to surgical correction and soon afterward. Pulmonary hypertension was mild (I) in 56.2%, moderate (II) in 25% and severe (III) in 18.8% cases. Though spirometric functions were lower with severe PH, these did not improve significantly 3 months later. But direct MBC improved significantly in grs. I and II, along with exercise VO2 and mean PAP. (DMBC:75.7 lit. to 91.8 lit: P less than 0.001; Exercise VO2 798 ml to 983 ml: P less than 0.001). Mean PAP 56.8 to 39.5 mm: P less than 0.001). Thus these functions may be used to objectively evaluate physiologic changes in cardiac surgical cases.

Effect of steam inhalation on mucociliary activity in patients of chronic pulmonary disease.

Increased mucociliary activity has been observed with several modalities, including inhalation which seems to achieve faster drug delivery. In patients of chronic lung disease, the mucociliary activity is known to be impaired. The effect of steam inhalation on mucociliary transport time was studied in these patients. It was found that steam inhalation improved mucociliary activity significantly (p < 0.001) in both groups receiving either only bronchodilators, or bronchodilators as well as steroids.

Early experience with sparfloxacin in tuberculosis.

Between December, 1996 and July, 1997, 14 patients of advanced tuberculosis with a mean history of prior treatment of 27.4 months were put on oral Sparfloxacin 200 mg daily. One case each had lumbar spine and pelvic bone disease with abscesses, one had subcostal abscess and another had subpulmonic effusion. The remaining 10 cases had moderate clinical illness with tuberculosis (meningitis (1), massive pneumonia (1)). There was an early dramatic response to the new regime, (Sparfloxacin given along with PAS, isoniazide (2), PH with R or Doxy (2), SHRZ (4), RH (1), RHZ (2), SHRE (1), and RH + Cy Eth (1)). The only side-effect complaint was nausea. The response was good (clinical 3+ or more: 11; Radiographic > 50%: 11; smear conversion: 12) in 12 cases; one case with tuberculous meningitis died seven weeks after a temporary improvement.

Respiratory distress in scorpion bite.

A 9 year old boy with history of scorpion bite presenting with respiratory distress is described.

Value of bronchoalveolar lavage in interstitial lung diseases.

Fifty-eight patients of interstitial lung diseases and 30 control patients were submitted to bronchoalveolar lavage (BAL) with flexible fibreoptic bronchoscopy. In 30 controls (with fluid recovery 61.7%) total cell count was 175 +/- 31/mm3 with macrophages 87.5 +/- 2.0%, neutrophils 7 +/- 1.9 and lymphocytes 5 +/- 0.6%. In idiopathic interstitial fibrosis (34 cases) these values were respectively 832 +/- 221/mm3, 47 +/- 5.5, 29 +/- 5.0 and 19 +/- 5 percent (significantly different P: less than 0.005, 0.001, 0.1 and 0.005 respectively from control. The results of bilateral lavages in 28 interstitial cases were similar. In other categories viz: sarcoidosis(8), macrophages were significantly fewer (61 +/- 10%: P less than 0.05) and lymphocytes significantly more (27 +/- 6.4%: P less than 0.05); in rheumatoid lung disease (4 cases) significantly fewer macrophages (45 +/- 5) were seen and 12 cases with methyl isocyanate exposure showed insignificant changes.

Effect of 3 week oxygen therapy on functional and haemodynamic parameters in chronic obstructive pulmonary disease.

Sixteen patients with advanced chronic obstructive pulmonary disease (COPD) and stable chronic respiratory failure (pO2 less than 60 mm Hg, pCO2 greater than 45 mm Hg) were given 2-3 L/min oxygen 18 hours/day for 3 weeks. These were serially assessed for changes in pO2, pCO2, ECG, chest radiographs and haemodynamics. Initially all patients were in grade IV heart failure. There was no change in lung function after oxygen treatment but right descending pulmonary artery diameter and cardiothoracic ratio decreased significantly (P less than 0.01), as also the height of the P wave in ECG (P less than 0.05). There were significant changes in mean pO2 (51.8 to 61.9 mmHg; P less than 0.01), pCO2 (55.3 to 47.6 mmHg; P less than 0.001), mean pulmonary artery pressure (41.8 to 34.5 mmHg; P less than 0.01) and pulmonary vascular resistance (PVR) (346.4 to 163.3 dynes; P less than 0.05). The initial (P less than 0.05) and 3 week (P less than 0.01) pO2 levels correlated with the right descending pulmonary artery diameter. The height of the P wave also correlated with pO2 (P less than 0.01). The changes in pO2 levels correlated with those of the PVR and pulmonary blood flow (P less than 0.05). Three week oxygen therapy resulted in objective improvement in advanced COPD cases.

Comparative study of amoxycillin and amoxycillin/clavulanic acid in lower respiratory infections.

A comparison of oral amoxycillin (500 mg tds) with amoxycillin/clavulanic acid (Augmentin; 750 mg tds) for 7 to 10 days was completed in 76 patients with lower respiratory infection. In another 9 patients, intravenous Augmentin alone was administered (1.2 g 8 hourly) for 3 days followed by oral doses as above for 7 days. In 50 (59%) patients the underlying chronic lung disease was bronchiectasis. Clinical improvement (1 + or more) was seen in 66% with amoxycillin, 60% with oral Augmentin and 56% with IV Augmentin. For radiographic improvement the respective figures were 47, 53 and 44 per cent. Bacteriologically, elimination was seen in 8% with amoxycillin and 45% with Augmentin (P less than 0.01), while partial success was seen in 16 and 24 per cent respectively. While for gram positive organisms, both drugs were similar in efficacy, for gram negative strains the overall success was 27% with amoxycillin and 67% with Augmentin. The main organisms isolated were Str pneumoniae (12), Klebsiella (41), Pseudomonas (21), E coli (9), Haemophilus (7) and Staph aureus (6). For bacteriologic sensitivity and consequent success, Augmentin may be superior in respiratory infections.

Comparative study of platelet histamine and serotonin with their corresponding plasma oxidases in asthmatics with normals.

OBJECTIVE: Asthma is well controllable but non-curable disease. Exact pathophysiology involved is unresolved till today. Role of allergic hypersensitivity reaction in asthmatic on-set is well established. Present work is an effort to elucidate some basic points of unresolved pathophysiology of asthma taking platelets as marker. MATERIAL AND METHODS: A group of 52 normal human subjects in the age group of 20-60 years were studied for platelet histamine and serotonin levels and also for their plasma metabolising enzymes diamine oxidase (DAO) and monoamine oxidase (MAO). The data was collected for 79 asthmatic patients at different stages of asthma and accordingly were studied as four different groups of seventy nine asthmatics those were on regular treatment and were comfortable with drugs and were free from symptomatic attack formed gr. I; these (79) patients were followed-up during their symptomatic phase (gr. II) and same (79) patients immediately after their recovery from symptomatic stage studied as gr. III members. All the 79 asthmatic patients fall in gr. I, II and III in a serial manner i.e. all (n = 79) in each group. A separate group of thirty seven patients with known history of asthma but were symptom free and also off drugs for last 2-4 years formed gr. IV. RESULTS: Results showed mean platelet count in asthmatics at all four stages were in the normal range but were slightly low in comparison with normals. Both the enzymatic levels (DAO and MAO) in gr. I, II and III were significantly higher than normals but were same in the case of gr. IV patients. Low levels of platelet biogenic amines were observed in asthmatics (gr. I to gr. IV) than normals. CONCLUSIONS: Thus, study parameters showed significant difference in asthmatics and normals. Findings of the study have been utilized to understand unanswered hypersensitivity shown by the asthmatics over normal individuals (non-asthmatics).

Air pollution related respiratory morbidity in central and north-eastern Bombay.

A study of 4 comparable communities in central & northeastern Bombay (2 each) among randomly matched 349 subjects in 1988-9, along with ambient sulfur dioxide (SO2), Nitrogen dioxide (NO2) & suspended particulate matter (SPM) air monitoring was carried out. The levels in winter were higher particularly for SO2 in Parel (upto 584 micrograms) in Maravali; Deonar showed lower pollution. There were inter-area differences for housing, income, residential history but age-sex differences were small; these were reduced by matching. Clinical respiratory symptoms were higher in Parel & Maravali (cough 12% and 11.2%, dyspnoea 17% & 13.3% respectively). Cardiac problems are commoner in Parel (11.0%). Smoker had cough more often but not dyspnoea. Maravali had a high prevalence for headache and eye irritation (9.5%). Those using kerosene suffered more than those using gas (22.2% as compared to 9.2%) Lung functions (FVC, FEVI) were lowest in Parel for males and in Maravali for females. Expiratory flow rates were lower at Dadar and then at Maravali. Despite lower SO2 pollution, Maravali residents suffered equally as in Parel. This may be due to added effect of diesel exhausts (NO2, SPM) or other unmeasured chemicals.

Changes in bronchoalveolar lavage and lung function in rheumatoid arthritis. A controlled study.

A comparative study of bronchoalveolar lavage was done in 30 patients with chronic rheumatoid arthritis and 30 age matched controls. Twelve patients had clinical lung disease (group I), 11 had lavage changes (group II) and 7 showed no abnormalities (group III). In group I, there was lower lung functions, tendency to older age and slightly longer history. There were no differences between the three groups (63% positive) in RA factor positivity. In the controls, lavage showed 67.3% return, 154.5 cells/cmm, 92.8% macrophages, 5.2% lymphocytes, 1.9% polymorphs and 0.2% eosinophils. In contrast, group I patients showed more polymorphs (10.3 +/- 8.3%) and group II more lymphocytes (14.5 +/- 18.7%; P less than 0.05). Thus, in chronic rheumatoid arthritic patients, bronchoalveolar lavage abnormalities may occur alone or in association with radiographic and functional abnormalities.

Role of metronidazole in improving response and specific drug sensitivity in advanced pulmonary tuberculosis.

One hundred and thirty-seven patients of advanced pulmonary tuberculosis were randomly allocated to receive metronidazole 400mg tid (76) or placebo (61) for 2 months in a single blind study. All received streptomycin 0.75 g,INH 30 mg and rifampicin 450 mg daily as standard antitubercle treatment. There were no significant pretreatment differences, among both groups. Compared to placebo group there was superior clinical improvement in metronidazole treated group at 4 and 8 weeks (81% vs 53%-P less than 0.05; 87% vs 72%-P less than 0.05 respectively), greater sputum reduction at 4 weeks (49% vs 9%-P less than 0.001) greater radiologic improvement at 4 weeks (60% vs 43%-P less than 0.01) and a better antituberculous drug sensitivity. Metronidazole seems to have beneficial adjuvant role in the drug treatment of tuberculosis. This may improve response in advanced cases.