A double-blind, randomized, placebo-controlled trial of the short-term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men.

AIM: To determine the short-term effect of vitamin D(3) supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men. SUBJECTS AND METHODS: A double-blind randomized controlled trial was conducted at a tertiary care facility in which 100 male volunteers aged > or = 35 years received three doses of vitamin D(3) (120,000 IU each; supplemented group) fortnightly or placebo (control group). Hepatic fasting insulin sensitivity [homeostasis model assessment (HOMA), quantitative insulin-sensitivity check index, HOMA-2], postprandial insulin sensitivity [oral glucose insulin sensitivity (OGIS)], insulin secretion (HOMA%B, HOMA2-%B), lipid profile and blood pressure were measured at baseline and at 6 weeks' follow-up. RESULTS: Seventy-one of the recruited subjects completed the study (35 in supplemented group, 36 in control group). There was an increase in OGIS with supplementation by per protocol analysis (P = 0.038; intention-to-treat analysis P = 0.055). The age- and baseline 25-hydroxyvitamin D level-adjusted difference in change in OGIS was highly significant (mean difference 41.1 +/- 15.5; P = 0.01). No changes in secondary outcome measures (insulin secretion, basal indices of insulin sensitivity, blood pressure or lipid profile) were found with supplementation. CONCLUSION: The trial indicates that vitamin D(3) supplementation improves postprandial insulin sensitivity (OGIS) in apparently healthy men likely to have insulin resistance (centrally obese but non-diabetic).

Glucocorticoid receptors in bronchoalveolar lavage fluid in sarcoidosis. A preliminary report.

Glucocorticoid receptor (GR) content was measured in bronchoalveolar lavage fluid (BALF) cells of 20 untreated patients with sarcoidosis. A significantly higher (p less than 0.001) lymphocyte count and GR content of BALF cells was noted in patients with sarcoidosis as compared to normal volunteers. The GR content correlated positively with lymphocytes (%) (r = 0.6; p less than 0.01) and was significantly higher (p less than 0.001) in patients who showed roentgenographic improvement, physiologic improvement, and improvement in both parameters compared to those who did not show improvement. Above findings suggest that the GR content of BALF cells is increased in sarcoidosis and a major contribution to this may be made by the lymphocytes.

Bronchoalveolar lavage in pulmonary tuberculosis: a decision analysis approach.

We assessed the utility of bronchoalveolar lavage (BAL) in the diagnosis of pulmonary tuberculosis (PTB) in 50 consecutive HIV-negative patients with clinical and radiographic findings suggestive of PTB, but with negative microscopy for acid-fast bacilli (AFB) on sputum smear. Patients were grouped, using a scoring system, into relative likelihoods of having PTB (I-IV, in descending probability). Patients were started on anti-tuberculosis treatment according to the BAL results. Bacteriological diagnosis of PTB was confirmed in 22/50 BAL; 11 (91.6%), seven (37%) and four (40%) of groups I-III, respectively. In 13 cases, an early diagnosis of PTB was made by positive microscopy for AFB on BAL; an alternative diagnosis was made in six cases (bacterial pneumonia 4, carcinoma 2). A decision analysis model was created to assess the overall utility of BAL. This suggested that in a region of high PTB prevalence, and when the clinical diagnosis of PTB is likely, empirical treatment is the best course of action, with BAL being reserved for further investigation of non-responders. Early BAL should be considered when the diagnosis of PTB is uncertain.

Clinical profile, laboratory characteristics and outcome in miliary tuberculosis.

We report a retrospective series of 100 non-HIV adult patients with miliary tuberculosis (MTB) treated in a tertiary care centre. There were 51 males. Their mean age was 35 years. Predisposing conditions existed in 34. Twelve patients had larger-than-miliary (> 2 mm) shadows in their chest roentgenograms. Five presented with acute respiratory failure, and early treatment cured four of them. Hyponatraemia occurred in 42/60 patients (70%) for whom values were available. Twelve patients (12%) died of MTB. Temperature > or = 39.3 degrees C (p < 0.01), hypoalbuminaemia (p < 0.01), hyponatraemia (p < 0.001), history of vomiting (p < 0.001) and presence of crepitations on auscultation (p < 0.001) were independent predictors of mortality. Diagnosis of MTB is difficult even in an endemic area, as the clinical symptoms are non-specific and the chest roentgenograms do not always reveal classical miliary changes. A high index of clinical suspicion and diligent efforts in confirming the diagnosis are needed, as early therapy yields good results.

Dyspnoea, lung function & respiratory muscle pressures in patients with Graves' disease.

To understand the pathophysiology of dyspnoea in patients with hyperthyroidism, lung function, maximum inspiratory, expiratory respiratory muscle pressures (MIP and MEP) and intensity of dyspnoea (after six minutes walking test) were recorded in 12 consecutive patients with active Graves' disease. Reassessment was done after achieving euthyroidism with 8-12 wk of carbimazole therapy. Patients covered similar distance during 6 min walking before and after carbimazole therapy. However, there was a significant reduction in dyspnoea following euthyroidism. This was accompanied by significant decrease in respiratory rate, minute ventilation, forced expiratory volume in one second (FEV1%) and improvement in the forced vital capacity (FVC). No significant changes in tidal volume (TV) and maximum-midexpiratory flow rates (MMEFR), MIP and MEP were observed. Lung function parameters, MIP and MEP did not correlate with the severity of dyspnoea. Serum T4 levels correlated inversely with the distance covered during 6 min walking test, MIP and MEP. To conclude, increased breathing effort in presence of reduced FVC may lead to dyspnoea during hyperthyroid phase in patients with active Graves' disease. Lack of correlation between the severity of dyspnoea and abnormalities in lung function suggests that other mechanisms of dyspnoea may also operate in these patients.

Postoperative pulmonary complications in patients with preoperative lung disease.

A prospective study was carried out on the incidence of pulmonary complications in 728 patients who underwent major surgical procedures at a reputed hospital in New Delhi. These patients were preoperatively assessed on the basis of history, clinical examination and bedside pulmonary function tests including PEFR, VC, FVC and FEV1. On the basis of these criteria, 212 patients had significant preoperative pulmonary disease, while 516 had normal lung functions. Postoperative pulmonary complications developed in 7.69 per cent of the patients. They were more frequent in smokers (P < 0.001) and in those with preoperative pulmonary dysfunction (P < 0.001). Their incidence was greater following thoraco-abdominal and musculoskeletal and miscellaneous operations compared to lower abdominal surgery (P < 0.001). The incidence was also higher following exposure to general anaesthesia compared to regional anaesthesia (P < 0.05). Pneumonia and atelectasis were the most common postoperative pulmonary complications. It was observed that the recovery of pulmonary functions was delayed in patients who developed postoperative pulmonary complications.

Immunologic & pulmonary function abnormalities in tropical pulmonary eosinophilia.

Twenty six patients (24 males and 2 females) with tropical pulmonary eosinophilia (TPE) were studied. Arterial blood gas analysis, pulmonary functions, peripheral blood examination and bronchoalveolar lavage (BAL) were performed. Peripheral blood and BAL fluid analyses were performed in healthy volunteers. Pulmonary functions revealed a mild restrictive ventilatory defect with airways obstruction. Mild hypoxaemia was observed on arterial blood gas analysis. Serum immunoglobulins IgG (P < 0.01), IgA (P < 0.001) and IgM (P < 0.001) were significantly raised as compared to normal controls. Serum complement (C3) level was higher, however, it was not significantly different as compared to normal controls. Serum haemolytic component of the complement (CH50) was significantly higher (P < 0.001) in patients with TPE compared to normal control subjects. The immunoglobulins IgG, IgA and IgM in the BAL fluid were significantly (P < 0.001) increased as compared to normal controls. The fibronectin (FN) level was also significantly increased (P < 0.001) in the BAL fluid. It is concluded that patients with TPE have mild restrictive ventilatory defect with airways obstruction and mild hypoxaemia. They have eosinophilic alveolitis with increased levels of immunoglobulins in the peripheral blood and BAL fluid. The significance of elevated FN in the BAL fluid is not clear and serial estimations may have to be done in order to clarify its role in the pathogenesis of fibrosis in chronic TPE.

Effect of inhalation of salbutamol, beclomethasone dipropionate & ipratropium bromide on mucociliary clearance in some patients with chronic stable bronchial asthma.

BACKGROUND & OBJECTIVES: Asthma is now regarded as an inflammatory disease and bronchial inflammation may disrupt mucociliary function. Inhaled drugs may act by improving mucociliary function. The aim of the study was to investigate the effect of salbutamol, ipratropium bromide and beclomethasone on mucociliary clearance in patients with chronic stable asthma and to compare the efficacy of these drugs on mucociliary clearance. METHODS: Ten patients with chronic stable asthma were enrolled in the study, but two patients did not complete the study. Patients with bronchial asthma were chosen on clinical grounds. (99m)Tc phytate radioaerosol generated through a nebulizer, was given to each patient on four days. After each administration the radioactivity over the thorax was constantly measured in sequential frame mode for 120 min. Radioactivity in the thorax was also measured after 24 h. A base-line pulmonary function test with reversibility was obtained. Salbutamol, ipratropium bromide, beclomethasone dipropionate and placebo inhalation were given randomly to each patient on four days. RESULTS: The mean age of patients (n = 8) was 36 +/- 9.3 yr and mean duration of symptoms was 5 +/- 6.6 yr. There was no visual impression that mucociliary clearance was enhanced with any of the drugs. The time activity curves did not show any visually recognisable change in slope. In only one patient the curve tended to show a steeper slope with ipratropium inhalation. In the rest of the patients the curves showed no difference at all with medication when compared with placebo. All the quantitative indices analyzed by two-way ANOVA at the end of one and two hours were comparable for the three test drugs and placebo. None of the three test drugs demonstrated statistically significant mucociliary clearance effect compared with placebo. However, the temporal difference in airways clearance efficiency (ACE) was significant with beclomethasone and ipratropium bromide. INTERPRETATION & CONCLUSION: Inhalation of any of the three drugs tested did not produce any immediate improvement in mucociliary clearance as compared to placebo in patients with stable bronchial asthma suggesting the need for further studies using higher doses of drugs for longer duration in a large sample.

Effect of corticosteroid treatment on various serological & bronchoalveolar lavage abnormalities in patients with sarcoidosis.

Effect of daily oral prednisolone treatment was studied in 29 patients with pulmonary sarcoidosis. Twenty normal control subjects were also studied. Pretreatment absolute lymphocyte counts and proportion of lymphocytes in peripheral blood were significantly lower in patients with sarcoidosis as compared to normal controls. Total cell count and the proportion of lymphocytes in bronchoalveolar lavage (BAL) fluid were significantly higher in sarcoidosis. The proportion of CD3+ and CD4+ was significantly lower in peripheral blood and higher in BAL fluid in patients with sarcoidosis. Immunoglobulins (IgG, A and M) and complements (C3, C4 and CH50) were significantly higher both in peripheral blood and BAL fluid. Patients with sarcoidosis were treated with daily oral prednisolone (30 mg/day). Repeat studies were performed after an interval of 4-6 months in 20 patients with sarcoidosis. A significant increase in absolute lymphocyte counts in peripheral blood and decrease in the proportion of lymphocytes in BAL fluid occurred with prednisolone treatment. Proportion of CD3+, CD4+ and B cells increased in peripheral blood and decreased in BAL fluid. Complement and immunoglobulin levels revealed a significant reduction in peripheral blood and BAL fluid. It is concluded that patients with sarcoidosis have peripheral blood lymphopaenia and lymphocytic alveolitis. They have increased levels of complement and immunoglobulins both in the peripheral blood and BAL fluid. All these abnormalities show significant improvement with prednisolone treatment.

Preparation & standardization of the goat lung surfactant extract.

Exogenous goat lung surfactant extract (GLSE) was obtained by chloroform-methanol extraction of the centrifuged lung lavage. Four lungs provided around 250 mg of surfactant. GLSE has a phospholipid content of 50 percent, cholesterol of 1.5 percent and protein content under 1 percent. The preparation was bacteriologically sterile and had a shelf life of at least one month at 4 degrees C. Endotracheal administration of surfactant (50 mg/kg) in a rat lung model rendered surfactant deficient by saline lavage, restored the compliance characteristics to normal, thus documenting biological activity of the preparation. The cost of a course of 2 doses of surfactant replacement therapy was estimated to be as low as Rs 500/-. The study opens up the possibility of surfactant replacement therapy for the management of neonatal respiratory distress syndrome in India by an indigenous product at an affordable cost.

The use of diagnostic bronchoscopy in lung cancer.

BACKGROUND: The role of fibreoptic bronchoscopy in the diagnosis of bronchogenic carcinoma is well established. However, in developing countries, where the burden of illness is large and diagnostic facilities are limited, only a small number of patients are diagnosed at a stage when they might benefit from operation. We felt it would be desirable to identify subsets of patients suspected of harbouring lung cancers, in whom bronchoscopy would have not only a high diagnostic yield but also provide useful information which might influence treatment, the patient's quality of life and duration of survival. METHOD: We analysed the records of 588 patients, who had been bronchoscoped for suspected lung cancer, over a period of 8 years at a tertiary referral centre in north India. The patients were divided into different clinical subgroups on the basis of their clinical and radiological presentation, and the diagnostic yield from bronchoscopy in each group was calculated. A decision analysis model was constructed and the expected value of clinical information was determined for each group. RESULTS: A tissue diagnosis was established by bronchoscopy in 177 (30%) patients and by additional investigations in 43 (7.3%) patients. A positive tissue diagnosis was obtained most often in patients with clinical and radiological evidence of pulmonary collapse (50%) and mass lesions (38-42%). Only 12% of patients with malignancy underwent resection and 70% of them belonged to the above two groups. The expected value of clinical information was greatest in patients with collapse (0.077) or mass lesions (0.067-0.065). CONCLUSIONS: A diagnostic work-up including fibreoptic bronchoscopy is indicated early in patients with collapse or mass lesions of the lung. Patients with non-resolving pneumonia, pleural effusion, metastatic disease and non-specific lesions on chest X-ray should receive a low priority for bronchoscopy.

Acetylator status, drug metabolism and disease.

Acetylation polymorphism, although discovered 40 years ago, still holds interest not only because many drugs and carcinogens are metabolized by acetylation in the liver but also because advances have been made in the understanding of the molecular genetics of acetylation. It is this genetic variation of drug metabolism that is one of the causes of inter-individual variation of the effect of a drug. Acetylation polymorphism relates to the metabolism of a number of arylamine and hydrazine drugs and carcinogens by cytosolic N-acetyltransferase--NAT2. In humans, 2 genes--NAT1 and NAT2--are responsible for the N-acetyltransferase activity. Studies have revealed several allelic variants of both NAT1 and NAT2. It has been suggested that some of these variants modify the individual susceptibility to disease.

Role of pleural fluid cholesterol in differentiating transudative from exudative pleural effusion.

BACKGROUND: Pleural fluid cholesterol has been reported to be useful in distinguishing between transudative and exudative pleural effusion. However, the difference in lipid profile between tubercular and non-tubercular pleural effusion has not been studied. METHODS: The lipid profile of pleural fluid in 50 patients with exudative (25 tubercular and 25 non-tubercular) and 25 with transudative effusion was studied. The diagnosis was based on clinical criteria and/or a positive diagnosis from another site. RESULTS: The criteria that best identified an exudative pleural effusion were pleural fluid cholesterol > or = 60 mg/dl, pleural fluid to serum cholesterol ratio > or = 0.4, pleural fluid triglyceride > or = 40 mg/dl and pleural fluid to serum triglyceride ratio > or = 0.3. Pleural fluid cholesterol had a sensitivity of 88% and a specificity of 100% for exudates with an accuracy of 92%. Pleural fluid to serum cholesterol ratio had a sensitivity of 98% and a specificity of 84%. These results were superior to the criteria proposed by Light et al. (sensitivity 98% and specificity 80%). CONCLUSION: Pleural fluid cholesterol estimation is an effective and cost-efficient method of differentiating exudative from transudative pleural effusion. The lipid profile does not help in diagnosing tubercular effusion.

Acute respiratory distress syndrome (ARDS) in miliary tuberculosis: a twelve year experience.

Miliary tuberculosis [MTB] is an uncommon but important treatable cause of acute respiratory distress syndrome [ARDS]. In this communication, six patients with MTB who developed ARDS in the course of their illness are described. The difficulties encountered in diagnosing MTB as a primary cause of ARDS are highlighted. The pathogenetic mechanisms of ARDS in MTB are briefly reviewed.

Chronic post traumatic thoracic aortic aneurysm mimicking a benign cyst.

Aneurysm of thoracic aorta may mimic cystic lesions like bronchogenic cyst or hydatid cyst. We report a case of chronic post traumatic thoracic aortic aneurysm in a young lady, initially diagnosed as benign cystic lesion. MRI scan of chest confirmed the diagnosis and subsequently surgical removal of aneurysm was done.

Endobronchial tuberculosis simulating lung cancer.

We describe an atypical presentation of endobronchial tuberculosis in a 45-year-old female who presented to us with a non-resolving pneumonia. Her radiological examination including contrast enhanced CT-scan suggested a diagnosis of bronchogenic carcinoma or adenoma. Gross bronchoscopic finding also favoured malignancy. But her bronchoscopic biopsy revealed caseating granulomatic lesion. She responded to antitubercular treatment.

Idiopathic pulmonary fibrosis: newer concepts and management strategies.

Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic fibrosing interstitial pneumonia limited to the lung and associated with the histologic appearance of usual interstitial pneumonia (UIP) on lung biopsy. It is characterized by progresive dyspnea, worsening of pulmonary function and radiographically, by patchy subpleural interstitial infiltrates with minimal ground glass appearance predominantly affecting the lung bases. The etiology is unknown and no therapy has been clearly shown to prolong survival. The diagnosis, which earlier was difficult to establish, is now based on guidelines of American Thoracic Society. Newer insight into its etiopathogenesis, particularly the mechanisms involved including T helper 1 (Th1) and T helper 2 (Th2) types of responses occurring after the initial and repetitive lung insults and the ineffectiveness of conventional modes of therapy has prompted clinicians worldwide to look for alternative modes of therapy. Conventional therapy for this disorder has been steroids and immunosuppressives. Immunomodulators (Interferon gamma 1b) and antioxidants (Glutathione and its precursor N-acetyl cysteine) are promising results in this, otherwise, uniformly fatal condition.

Effect of routine fiberoptic bronchoscopy and bronchoalveolar lavage on arterial blood gases.

Effect of conventional fiberoptic bronchoscopy (FOB) procedure (Group A, n = 10) and bronchoalveolar lavage (BAL) (Group B, n = 11) on arterial blood gases was studied in 21 patients. A significant fall in arterial oxygen tension (PaO2) with widening of alveolar arterial oxygen gradient D(A-a)O2 was observed during FOB (p < 0.001) and 30 minutes following the procedure (p < 0.001). Bronchoalveolar lavage was also associated with significant fall (p < 0.001) in PaO2 with increased D(A-a)O2 and this fall in PaO2 persisted for 30 minutes after the procedure (p < 0.01). None of the patients received oxygen during the procedures. None of the patients in either group developed bronchospasm. No change in arterial carbon dioxide (PaCO2) was observed in either group. Hypoxaemic encephalopathy developed in one patient in group A, hypotension and cyanosis developed in one patient each in group B. No mortality was encountered in the study. All the three patients with complications were excluded from final analysis. It was concluded from this study that both conventional bronchoscopy and BAL procedures were associated with significant hypoxaemia and supplemental oxygen should be given to all patients during the procedure and should be continued for at least 30 min. afterwards.

Diagnostic methods for tuberculosis.

Tuberculosis (TB) is a major public health problem especially in the third world countries. In India, it is estimated that at present there may be approximately 10 million persons suffering from radiologically evident pulmonary TB of whom about 2.5 million would be sputum positive. The number of deaths due to tuberculosis is estimated to be approximately 5,000,000 every year. Definitive diagnosis of tuberculosis depends on smear examination and culture of appropriate biological fluids. Only up to 50% of pulmonary and 25% of extrapulmonary TB are diagnosed by smear examination. Traditional culture methods take around 6 weeks before the diagnosis can be established. Chemotherapy for tuberculosis is prolonged, expensive and not free from serious side effects. If the diagnosis of TB is delayed, it leads to increases morbidity and in some cases mortality (e.g. tuberculous meningitis). Often the clinicians have to start therapy empirically. There is a great need, therefore, for tests which are highly sensitive and specific as well as rapid.

Prognostic scoring for critically ill hospitalized patients.

The objective of the study was to validate and refine the APACHE II (acute physiology and chronic health evaluation II) prognostic system in the Indian context. We prospectively collected data on 79 patients admitted in the medical intensive care unit. We have studied APACHE II and 11 other physiological variables and sought to improve the risk prediction by developing a new score to be governed by the rule of thumb at the bed side. The new score included the following five variables: pH and serum albumin at admission and heart rate, bilirubin and Glasgow coma scale at 48 hours. A score below 3.5 was independently associated with a statistically significant increase in the risk of hospital death. This model resulted in a pseudo r2 of 0.43 in comparison to pseudo r2 of 0.02 and 0.12 for APACHE II scores on the day of admission and after 48 hours, respectively.