Vocal cord dysfunction presenting as recurrent acute severe asthma.
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Biomedical subjects
Publications and source records attributed to S K Jindal.
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Steroid hormones have been implicated in the etiology and/or progression of epithelial ovarian cancer. As ovarian surface epithelial cells are growth inhibited by transforming growth factor beta (TGF-beta), we tested whether steroid hormones could regulate the expression of TGF-beta1 or its receptors in ovarian cancer cells, as assessed by quantitative reverse transcription-PCR. Treatment of ovarian cancer HEY cells with 500 nM 5alpha-dihydrotestosterone (DHT), but not estradiol-17beta or progesterone, for 60 h down-regulated the expression of mRNA for TGF-beta receptors I and II (TbetaR-I and TbetaR-II), betaglycan, and endoglin but had no effect on TGF-beta1 mRNA levels. Androgen receptor (AR) mRNA expression in HEY cells was compared to other ovarian cancer cell lines. OVCAR-3 cells expressed AR mRNA levels similar to that of androgen-responsive LNCaP prostate cancer cells, whereas SKOV-3 and HEY cells expressed only 3 and 0.01%, respectively. Western blot analysis and saturation binding assays confirmed the expression of AR protein in these three cell lines, but at the limit of detection in SKOV-3 and HEY cells. Treatment of SKOV-3 and HEY cells for 24 h with 1-50 nM DHT resulted in a dose-dependent down-regulation of TbetaR-II mRNA. The AR antagonist hydroxyflutamide did not reverse the effect of DHT on SKOV-3 cells but by itself down-regulated TbetaR-II mRNA. This apparent androgen-mimetic action of hydroxyflutamide and the ability of SKOV-3 and HEY cells to respond to DHT may be due to their expression of AR-associating protein 70, an AR co-activator reported to amplify AR transactivation and to result in agonist activity of AR antagonists. DHT was able to reverse TGF-beta1 growth-inhibitory action in SKOV-3 cells and in a primary culture of ovarian cancer cells derived from ascites. Thus, androgens may promote ovarian cancer progression in part by decreasing TGF-beta receptor levels, thereby allowing ovarian cancer cells to escape TGF-beta1 growth inhibition.
Thyroid function tests (serum levels of thyroxine-T4, triiodothyronine-T3 and thyroid stimulating hormone-TSH) were performed in fifty-eight men (mean age: 31.7 +/- 10.6 years; mean duration of lead exposure: 156.9 +/- 122.7 months). These subjects were exposed to lead either as petrol pump workers or automobile mechanics. The mean whole blood lead (Pb-B) levels were 2.49 +/- 0.45 micromole/l (51.90 +/- 9.40 microg/dl) in the lead exposed workers and were approximately 5 times higher than in the control (n = 35) subjects. No significant alteration was seen in their mean T3 and T4 levels as compared with the controls. Interestingly, T3 was significantly lower with the longer (210 months) exposure time in comparison with the group having shorter (29 months) exposure duration. The mean TSH levels were significantly (p < 0.01) higher in workers exposed in comparison with the control group. This rise in TSH was independent of exposure time, but it was definitely associated with the Pb-B levels. The increase being more pronounced with mean Pb-B levels of 2.66 +/- 0.2 micromole/l (55.4 +/- 4.25 microg/dl) when compared with the group having mean levels of 1.51 +/- 0.30 micromole/l (31.5 +/- 6.20 microg/dl). The rise is TSH associated with Pb-B levels was only statistical valid, however, the levels fall within the normal laboratory range. We thus conclude that the Pb-B levels of > or = 2.4 micromole/l (50 microg/dl) could enhance the pituitary release of TSH without having any significant alterations in the circulating levels of T3 and T4.
PURPOSE: To compare the diagnostic yield of fine-needle aspiration biopsy (FNAB) and cutting needle biopsy in thoracic lesions. MATERIAL AND METHODS: Thirty patients with thoracic mass lesions were subjected to ultrasound-guided co-axial FNAB and cutting needle biopsy using 0.7 mm aspirating and 1.0-mm cutting needles, respectively. The diagnostic yield of the individual modalities was compared with the combined yield. RESULTS: A conclusive diagnosis was obtained in 76.6% (n=23) of patients by FNAB and in 66.6% (n=20) by cutting needle biopsy. The combined diagnostic yield of FNAB and cutting needle biopsy was 93.3% (n=28) with a significant statistical difference (p<0.03) as compared to cutting biopsy alone. Of the patients, 23.2% (n=7) had benign and 76.6% (n=23) malignant aetiologies. The diagnostic yield of FNAB versus cutting needle biopsy in benign lesions was 57.1% (n=4) and 100% (n=7), respectively. The diagnostic yield of FNAB versus cutting needle biopsy in malignant lesions was 82.6% (n=19) and 56.5%, (n=13). Two patients remained undiagnosed by either modality. There were no complications. CONCLUSION: FNAB and cutting needle biopsy are complementary to each other and attempts should be made to obtain small tissue cores in addition to routine cytologic specimens in diagnosing thoracic lesions, especially in benign pathologies. US provides a safe guidance modality for lesions abutting the chest wall.
A 30-year-old woman was examined for a history of exertional breathlessness, swelling of her feet, and a mild dry cough of 4 to 5 months' duration. Her symptoms developed during the last month of her pregnancy, with gradually increasing dyspnea, swelling of the feet, and reduced urinary output. There was no history of expectoration, hemoptysis, chest pain, or tuberculosis. General physical examination showed no evidence of clubbing of the nails or lymphadenopathy. Chest auscultation revealed a few end-inspiratory crepitations at both lung bases. Bronchial alveolar lavage showed calcium particles, whereas results of the transbronchial lung biopsy were consistent with alveolar microlithiasis.
OBJECTIVE: To assess the utility of static lung pressure-volume measurements in identifying and categorizing pulmonary function test defects in survivors of acute respiratory distress syndrome (ARDS). DESIGN: Cross-sectional. SETTING: Pulmonary function laboratory at a tertiary referral hospital in northern India. PATIENTS: Six survivors of ARDS reporting for their first follow-up visit after discharge. MEASUREMENTS AND MAIN RESULTS: Spirometry and whole body plethysmography were performed to evaluate lung volumes and to collect static lung pressure-volume data; the latter were subjected to monoexponential analysis. Three patients had a restrictive ventilatory defect as evidenced by diminished vital capacity and total lung capacity, but only one had reduced static lung compliance. The other two patients had reduced recoil pressure at total lung capacity, suggestive of respiratory muscle weakness. Two other patients with normal lung volumes had reduced static lung compliance. Exponential analysis of pressure-volume data in the three patients with reduced static lung compliance was consistent with reduced distensibility and loss of lung units in one patient each. Additionally, two patients had high values for shape constant of the exponential curve, indicative of air space distention. CONCLUSIONS: Detailed analysis of static pressure-volume data can identify pulmonary function abnormality and categorize the dominant mechanism responsible for restrictive ventilatory defects in survivors of ARDS, even in patients with normal lung volumes. In addition to lung fibrosis, neuromuscular weakness also contributes to decline in pulmonary function.
Sarcoidosis is seen in different parts of India and other developing countries with almost similar frequency as in the West. It was largely due to lack of awareness and non-availability of investigations for diagnosis that the disease was reported to be rare in the past. A combination of clinical, radiologic, and histologic criteria are used to diagnose sarcoidosis. A confident exclusion of other causes of granuloma formation, especially tuberculosis, is required. Absence of mycobacteria and of caseation in the histologic specimens and presence of skin anergy to tuberculin help make a diagnosis. Transbronchial lung biopsy obtained with the help of fiberoptic bronchoscopy is positive in about 80% of patients. Corticosteroids are used to treat patients with symptoms and those showing active organ involvement. Aggressive treatment is required for patients with acute and severe pulmonary, cardiac, ocular, or neurologic involvements.
Prevalence of asthma was calculated using a Hindi adaptation of the International Union Against Tuberculosis and Lung Disease (IUATLD)-1984 questionnaire. The questionnaire was administered to patients with and without asthma to select specific items to define asthma. Questionnaire validity was tested against physician-diagnosed asthma in 753 individuals in the field, with sensitivity and specificity of 63.1% and 98.8%, respectively. The field prevalence study was conducted among 958 men and 1158 women. True population prevalence, calculated from the observed prevalence using specificity and sensitivity of the questionnaire, was 3.94% in urban men, 3.99% in rural men, and 1.27% in both urban and rural women.
We measured height and arm span of 400 males and 231 female subjects between 16-83 years of age. Arm span exceeded height in 82.6% subjects. Mean height to arm span ratio was 0.9711 and 0.9816 in males and females respectively, and was not significantly correlated with age. Linear regression equations were generated for both sexes for prediction of height from arm span and age. The use of height to arm span ratio was found to be a less suitable method than the use of regression equations in estimating height from arm span.
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History of cancer among first degree relatives was obtained in 124 patients with bronchogenic carcinoma [probands] and 248 controls, and differences in familial aggregation evaluated by calculation of odds ratio [OR] and their 95 percent confidence intervals [95% CI]. Probands were more likely than controls to have relatives with cancers [OR 1.27, 95% CI 0.49-3.10], both among smokers and nonsmokers [OR 1.31, 95% CI 0.27-6.79 and OR 1.21, 95% CI 0.12-6.16 respectively]. Sisters of probands were particularly at a higher risk [OR 8.72, 95% CI 0.85-430.08]. A genetic component, possibly independent of smoking habits, may be important in the causation of lung cancer.
The aim of this study is to assess the relationship between exposure to environmental tobacco smoke (ETS) and lung cancer in non-smokers, a case-control study among lifetime non-smokers was conducted in Chandigarh, India. Cases consisted of 58 non-smoking histologically confirmed lung cancer patients; two controls for each case were selected, one among other patients admitted to the wards and one among the visitors to hospital patients. Subjects were asked about ETS exposure from different tobacco products in childhood and in adulthood at home, at the work place and in vehicles. Multivariate logistic regression analysis was used to assess the effects of the ETS exposure variables on lung cancer. Exposure to ETS during childhood was strongly associated with lung cancer (odds ratio (OR) = 3.9; 95% confidence interval (CI) = 1.9-8.2), the effect mostly arising from exposure to cigarettes smoke. The excess risk was observed with either a smoking father or mother. An increasing risk was found with increasing number of smokers and duration of exposure. Restricting the analysis to women produced higher estimates of the risk. No increased risk was found with exposure to a smoking spouse, except for those exposed only to cigarette smoke (OR = 5.1; 95% CI = 1.5-17). A weak association was seen between lung cancer and ETS exposure at the workplace, which increased with the number of years of exposure. Exposure in vehicles also was detected as a risk factor for lung cancer in non-smokers. This study suggests that ETS exposure may be a strong risk factor for lung cancer also in India, a country with low prevalence of smoking and, therefore, low rates of lung cancer. Other studies need to be conducted in similar settings to confirm the role played by ETS exposure early in life in the causation of lung cancer.
Management of interstitial lung disease, especially idiopathic pulmonary fibrosis, is both difficult and unsatisfactory. In many patients, only supportive therapy can be instituted. Attempts have been made to use anti-inflammatory therapy to reverse inflammation, provide symptomatic relief, stop disease progression, and prolong survival; the results of such treatment have varied from no improvement to significant prolongation of survival. Corticosteroids are the most frequently used anti-inflammatory agents. Cytotoxic drugs, such as oral azathioprine or intermittent intravenous cyclophosphamide, have also been shown to be effective both alone and in combination with low-dose oral corticosteroids. Of the other antifibrotic drugs that have been used, colchicine seems to provide some benefit. It is especially useful in aged persons and those with corticosteroid-induced problems or concomitant illnesses that are likely to be worsened by steroids. Anti-inflammatory therapy is costly to administer and monitor, particularly in the developing world. It is therefore important to consider these issues before instituting treatment. Younger patients and patients with less-severe disease of recent onset are most likely to respond to treatment. Similarly, patients with lymphocytic alveolitis or desquamative interstitial pneumonia respond better. Despite the use of newer strategies for treatment, the overall prognosis for patients with interstitial lung disease has not really changed, and the median population survival remains almost the same as it was about 30 years ago.
Respiratory physiological deadspace (VDphys) during normocapnic ventilation under anaesthesia was studied in 253 patients scheduled for elective non-thoracic surgery. Subjects were ventilated with SERVO 900B ventilator using CO2 analyser 930 (Siemens-Elema Sweden) to adjust minute volume sufficient to maintain end-tidal carbon dioxide fraction (FECO2) around 5.5kPa with normocapnic confirmation using arterial blood gas analysis. VDphys was calculated using Enghoff's modification of Bohr's equation. VDphys and deadspace to tidal volume ratios (VD/VT) in male patients were 142.6 +/- 28.4 ml and 0.37 +/- 0.068 respectively and were significantly higher than that in females (119.4 +/- 35.6 ml and 0.36 +/- 0.067). Males had significantly higher VDphys/mass (2.5 +/- 0.68 ml.kg) compared with females (2.2 +/- 0.54 ml/kg, P < 0.001) but significantly lower body mass index (BMI) (20.67 +/- 3.2 in males and 22.47 +/- 4.1 in females, P < 0.001). VDphys showed positive correlation with weight, height and body surface area (BSA) but VDphys/kg showed negative correlation with BMI. Multiple regression analysis produced a best fit equation for VDphys = 9.7 + 64.3 x BSA + 13.51S where S = 1 for females and 2 for males.
STUDY OBJECTIVE: To evaluate if direct substitution of arm span for height during interpretation of spirometry data leads to any significant statistical or clinical differences in Indian adults, and to compare this method with the use of height estimated indirectly from arm span. DESIGN: Cross-sectional. SETTING: Respiratory laboratory of a tertiary referral hospital in North India. PARTICIPANTS: Two hundred twenty-eight subjects referred for spirometry. MEASUREMENTS AND RESULTS: Standing height and arm span were measured for all subjects. Spirometry measurements included FVC, FEV1, FEV1/FVC, peak expiratory flow, and maximal midexpiratory flow. Predicted values for each parameter were calculated separately for height, arm span, and height estimated from fixed height:arm span ratio. Results were classified into normal, obstructive, and restrictive defects for each height, arm span, and estimated height measurement, and any abnormality was categorized as mild, moderate, or severe. Arm span exceeded height in 182 (79.82%) subjects. Thirty-seven (16.2%) and 32 (14.0%) results were classified or categorized incorrectly when arm span and estimated height were substituted respectively, for actual height, with a kappa estimate of agreement 0.779 and 0.808, respectively; 17.4% and 11.0% normal results were classified, respectively, as restrictive defects using arm span and estimated height. Limits of agreement, which were almost equally wide for both sets of data, were more than the permissible intraindividual variability for FVC and FEV1. CONCLUSIONS: The substitution of arm span for height introduces statistically significant changes in spirometry results. Use of height estimated from arm span using fixed ratio also leads to misclassification of data, though less than that caused by use of arm span alone. Height estimated from arm span can be substituted for actual height in patients in whom height cannot be measured reliably. Where racial/ethnic norms for height and arm span correlation are not available, arm span is a reasonable surrogate for standing height.
An algorithm for diagnosis of pulmonary fibrosis in the tropical countries has been developed on the basis of the common causes of fibrosis, and the availability and feasibility of different diagnostic techniques in those countries. First, it is important to exclude common diseases such as the atypical or occult forms of bronchiectasis, pulmonary tuberculosis, and chronic bronchitis, which often overshadow interstitial pulmonary fibrosis. A good history and physical examination supplemented with chest radiography and simple lung function tests are generally enough to narrow down the list of causes of diffuse lung disease to interstitial pulmonary fibrosis. The real difficulty lies in identifying the idiopathic or "lone" forms from the secondary forms of pulmonary fibrosis. High-resolution CT is helpful in a large number of patients. Transbronchial lung biopsy is performed in a select population of patients. Open surgical or thoracoscopy guided biopsy is the gold standard, but is rarely required.
Gastroesophageal reflux (GER) is a common occurrence in patients with asthma. We performed a prospective study to detect GER in patients with asthma using pH monitoring. Twenty consecutive patients (mean age 48 +/- 14 yr, range 23-70; 13 men) with asthma of unexplained etiology were evaluated. Esophageal and gastric pH were studied both while introducing and pulling out pH probe. Upper GI endoscopy was done in all the patients before doing pH monitoring. Esophageal pH was recorded at 25 cm, 30 cm and 35 cm from the incisors. Mean esophageal pH values while introducing pH probe were 2.9 +/- 1.08 (0-5.1), 2.5 +/- 1.2 (0-5) and 1.6 +/- 1.5 (0-4.6) at 25 cm, 30 cm and 35 cm from incisors respectively. The gastric pH was 0.5 +/- 0.4 (0-2). While pulling out pH probe, pH values were 1.5 +/- 1.4 (0-4.7), 2.4 +/- 1.5 (0-5.1) and 2.9 +/- 1.4 (0-5.4) at 35 cm, 30 cm, and 25 cm from incisors respectively. Of 20 patients, 19 had pH of 4 or lower at 25 cm, 30 cm and 35 cm from incisors. The mean pH value was lower at 35 cm than at 30 cm and 25 cm (1.6 +/- 1.5 vs 2.5 +/- 1.2 and 2.9 +/- 1.08, p < 0.04). In conclusion majority of adults with asthma have silent GER as detected on pH monitoring.
Role of Parthenium hysterophorous as an allergen evoking bronchial hyper-responsiveness was assessed in twenty five adult patients with stable asthma and ten healthy controls. Assessment was made with the help of skin prick and bronchial provocation tests (BPT) using a commercially available Pathenium extract. Eleven patients (44%) of the study group had a positive skin reaction and 4 (16%) showed a significant fall in FEV1 and PEFR (p < 0.05) on bronchial provocation. In the control group only one patient (10%) had a positive skin test while there was none with a positive bronchial challenge. There was a significant fall in the mean values of FEV1 and PEFR over base line after the BPT in patients of asthma than controls. It is concluded that a significant proportion of bronchial asthma patients are sensitized to Parthenium hysterophorous and it may act as a cofactor in seasonal exacerbation of their symptoms.