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).

Changes in ventilatory function following surgery for bilateral abductor paralysis.

Management of bilateral vocal fold immobility continues to remain a challenge for the Otolaryngologist who attempts to create a balance between creation of an adequate airway and preservation of voice. The flow volume loop obtained by spirometry provides an ideal objective assessment tool to evaluate the results of surgery for this condition. Our experience in using peak inspiratory flow rate (PIFR) and forced inspiratory flow with 50% of vital capacity (FIF(50)) in the lung in assessing the results of surgery is described. Seventeen patients were included in the study. The surgical procedures performed included laser posterior cordectomy with partial arytenoidectomy, endoscopic arytenoidectomy and posterior cordectomy-Kashima's technique. Twelve out of 17 patients were successfully decannulated, a success rate of 70.6%. All patients except one showed an increase in mid-inspiratory flow rates and peak inspiratory flow rates. The mean increase in FIF(50) was 0.44 l/sec (52.6%) and the mean increase in PIFR was 0.41l/sec (39.77%). No statistically significant difference in improvement of inspiratory flow rates was observed between the three surgical procedures used in the study.

Plasma membrane calcium pump activity in rat pancreatic islets: an accurate method to measure its calcium-dependent modulation.

The aim of this study was to quantify the glucose modulation of the plasma membrane calcium pump (PMCA) function in rat pancreatic islets. Ca2+-ATPase activity and levels of phosphorylated PMCA intermediates both transiently declined to a minimum in response to stimulation by glucose. Strictly dependent on Ca2+ concentration, this inhibitory effect was fully expressed at physiological concentrations of the cation (less than 0.5 muM), then progressively diminished at higher concentrations. These results, together with those previously reported on the effects of insulin secretagogues and blockers on the activity, expression and cellular distribution of the PMCA, support the concept that the PMCA plays a key role in the regulation of Ca2+ signaling and insulin secretion in pancreatic islets.

Bronchoscopy in adults at a tertiary care centre: indications and complications.

Fibreoptic bronchoscopy (FOB) helps in visualisation of the endobronchial tree. Fibreoptic bronchoscopies were done in 429 cases between January 1999 and January 2000 [322 men (75.1%) and 107 women (24.9%)]. Patients were between 12 and 89 years of age (mean+/- SD = 49 +/- 15.1 years). Of which, 196 (45.7%) had lung cancer and 233 (54.4%) had non-malignant disease [Tuberculosis (TB) 26, miliary TB 16, non-resolving pneumonia 29, atypical pneumonia 10, bronchiectasis 11, aspergillosis 12, sarcoidosis 17, interstitial lung disease (ILD) 20, haemoptysis with normal chest x-ray 13 and miscellaneous 79]. In this series of 429 patients a significant number of patients (n = 127) presented with fever (38 malignant and 89 non-malignant disease, p < 0.0001), 137 had haemoptysis (74 malignant and 63 non-malignant disease, p < 0.01), 89 had chest pain (61 malignant and 28 non-malignant disease, p < 0.0001) and 29 patients presented with complaint of anorexia (21 malignant and 8 non-malignant disease, p < 0.003). High prevalence of lung lesions in the right upper lobe [10.4% (43 of 411)] and left main bronchus [12% (49 of 411)] was observed. Left upper lobe showed 8.7% (36 patients) lesions and right middle lobe showed 5.5% (23 patients) lesions. In 143 (34.8%) patients, FOB findings were normal. Out of 407 patients, FOB was suggestive of necrotic/nodular growth in 159 patients (39.1%), infiltrative growth in 8 patients (1.9%), and extrinsic compression was found in 39 patients (9.6%). In 143 patients (35.2%) no endobronchial growth was seen. Bronchial biopsy (BB) was performed in 162 (37.8%) patients, transbronchial lung biopsy in 56 patients (13.1%), bronchial washing for cytology in 350 patients (81.5%), bronchial washing for AFB in 302 patients (70.3%), bronchial washing for culture in 67 patients (15.6%), bronchial washing for fungus in 64 patients (14.9%) and Pneumocystis carinii infection was looked for in 6 patients (1.4%). Postbronchoscopy complications were recorded as follows: Early termination of FOB due to decreased O2 saturation in 10 cases (2.4%), postbiopsy bleeding in 5 cases (1.2%), post FOB fever in 5 cases (1.2%), chest pain in 7 patients (1.7%) and pneumothorax occurred in 2 patients (0.5%). FOB performed in outpatient setting is a useful and safe modality. Most patients in whom FOB was done in the present setup had suspected lung cancer. No major complications were encountered.

Domestic cooking fuel and lung functions in healthy non-smoking women.

OBJECTIVE: The objective of this study was to compare the pulmonary functions in healthy non-smoking women who used either biomass or liquified petroleum gas (LPG) as their sole cooking fuel. The effects of passive smoking, ventilation, over crowding and cooking index were also taken into account. METHODOLOGY: The study was conducted over a period of two years from January 1994. One hundred healthy non-smoking women were included 50 cooked solely with biomass and 50 cooked with LPG. A standardised respiratory symptoms questionnaire was administered to all the subjects and spirometry was carried out. RESULTS: Passive smoking showed no significant difference between the two groups. No statistically significant differences was found in lung functions in the two groups except for the PEFR, which was significantly lower (P < 0.01) in women using biomass. No correlation was observed between different variables and pulmonary functions. The step-wise multivariate linear regression analysis showed no correlation between cooking fuel and the pulmonary functions. CONCLUSION: The absence of the expected adverse effects of biomass on pulmonary functions was possibly due to better ventilation in the kitchens of subjects in the biomass group compared to previous studies.

Risk factors associated with preterm labour.

A Prospective case control study was conducted in a tertiary hospital in Northern India to determine the risk factors associated with preterm labour. Ninety four consecutive patients with preterm spontaneous labour were selected as cases and 188 patients with term spontaneous labour as control. The incidence of preterm labour was found to be 23.3%. The cases were older, shorter and lighter than controls. They had lower body mass index (BMI) and mid arm circumference (MAC). They belonged to significantly lower income group and their educational status was lower. Mean pregnancy order was higher and mean parity was lower amongst the cases. Mean birth weight and apgar score of the babies were lower. Maternal weight <45 kg (OR 4.9), height <150 cm (OR 3.4), BMI <19 kg/m2 (OR 2.91), MAC <20 cm (OR 7.78), education <5 year (OR 2.73), income <2000 rupees (OR 5.05) and birth interval <12 months (OR 6.39) were significant risk factors for preterm labour.

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 single inhalation of a salbutamol, ipratropium bromide and beclomethasone on mucociliary clearance in patients with chronic obstructive airway disease.

BACKGROUND: Chronic obstructive airway disease (COAD) is associated with hyperplasia and hypertrophy of the mucus producing glands. The beneficial effect of inhaled drug may be due to improved mucociliary function. The present study was done to evaluate the effect of salbutamol, ipratropium bromide and beclomethasone dipropionate inhalation on mucociliary clearance in patients with COAD. METHODS: Ten patients of COAD were taken up, two patients however did not complete the study. Salbutamol, ipratropium bromide, beclomethasone dipropionate and placebo inhalation were given randomly to each patient on four separate days. Radioaerosol inhalation lung cine-scintigraphy after inhalation of the different drugs was followed up to two hours and than after 24 hours. RESULTS: There was no significant visually noticeable increased mucociliary clearance on any of the days. Two patients showed definite steep slope in the time activity curves with salbutamol as compared to other drugs or placebo. All the quantitative indices analysed at the end of one hour and two hours for the three drugs were comparable to placebo. CONCLUSIONS: A single dose of inhaled salbutamol, ipratropium bromide and beclomethasone dipropionate has no appreciable effect on mucociliary clearance in patients with COAD.

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.

Pulmonary functions in patients with epidemic dropsy.

Pulmonary functions were performed in thirteen patients with epidemic dropsy. The epidemic occurred in Delhi in 1998 during which 102 patients with epidemic dropsy reported to our medical unit. Other investigations included chest radiograph, ECG, liver and renal function tests. There was a restrictive ventilatory defect with diminution of diffusion capacity for carbon monoxide in these patients. Echocardiogram was done in seven of these patients and was normal. The cause of breathlessness and restrictive ventilatory defect is likely to be non-cardiogenic pulmonary oedema.

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.

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.

Sleep disordered breathing in chronic obstructive pulmonary disease.

We prospectively studied sleep disordered breathing in 50 consecutive patients (39 males) with chronic obstructive pulmonary disease (COPD) with chronic respiratory failure (CRF) (n=33) and without CRF (n=17) by performing polysomnography. Patients with CRF had a lower mean nocturnal oxygen saturation (SaO2 %) (88.6+/-6.7 vs. 96.3+/-0.8; p=0.0001) and a lower minimal nocturnal SaO2 (73.6+/-12.0 vs. 84.3+/-7.3; p=0.002) compared to those without CRF, suggesting that patients with CRF tend to have more severe drops in nocturnal SaO2. Patients with CRF also had a lower FEV1 (% predicted) (p=0.01) and PEFR (% predicted) (p=0.031) compared to those without CRF suggesting an indirect relation to the oxygen saturation. Other pulmonary functions were comparable between both the groups. Among patients with and without CRF, the total sleep time (minutes); the rapid eye movement (REM) stage (% of total sleep time); the non-rapid eye movement (NREM) stage (% of total sleep time) were comparable (p=NS). Only three of the 50 patients with COPD had a significant (>5) apnea-hypopnea index (AHI) (total no. of apneas + total no. of hypopneas/ total sleep time [(hours) = AHI] and these three patients had a mean BMI = 27.7 which was higher than the mean BMI of the whole group (21.1). The AHI was comparable in patients with and without respiratory failure. Multiple regression analysis revealed a positive correlation between AHI and the neck circumference (r=0.41; p=0.005) and BMI (r=0.31; p=NS). There was a small but statistically insignificant negative correlation between AHI and neck length (r= -0.28; p=NS). We conclude that, BMI per se contributes to the AHI and nocturnal desaturation in patients with COPD.

Outdoor air pollution and emergency room visits at a hospital in Delhi.

Several reports from large metropolitan cities have indicated significant association between acute morbidity and mortality from cardio-respiratory disorders and daily levels of major pollutants in the ambient air. Despite the wide-spread public concern about the adverse health effects of air pollution, there is substantial uncertainty regarding the effects of these pollutants at a concentration typical of Delhi, which is one of the ten most polluted cities in the world and the most polluted city in India. This study was undertaken to correlate the daily levels of various pollutants with the number of patients visiting the All India Institute of Medical Sciences (AIIMS, New Delhi) casualty for aggravation of certain defined cardiorespiratory disorders. Daily counts of patients visiting the emergency room of the AIIMS for acute asthma, acute exacerbation of chronic obstructive airway disease (COAD) and acute coronary event was obtained in prospective manner from January 1997 to December 1998. Daily mean levels of ambient CO, NOx and SO2 were monitored along with temperature and humidity. Data was analysed using one day time lag for events of interest. Time series analysis was undertaken using Poisson regression and population averaged general estimation equation, correcting for auto-correlation, days of the weak and season. The ambient levels of pollutants exceeded the national air quality standards on most of the days, over the two year period. Further, emergency room visits for asthma, COAD and acute coronary events increased by 21.30%, 24.90% and 24.30% respectively on account of higher than acceptable levels of pollutants. It is concluded that there is considerable burden of cardiorespiratory diseases in Delhi due to high levels of ambient air pollution.

Enhanced crystallization of the Cys18 to Ser mutant of bovine gammaB crystallin.

The cysteine residues of the gamma crystallins, a family of ocular lens proteins, are involved in the aggregation and phase separation of these proteins. Both these phenomena are implicated in cataract formation. We have used bovine gammaB crystallin as a model system to study the role of the individual cysteine residues in the aggregation and phase separation of the gamma crystallins. Here, we compare the thermodynamic and kinetic behavior of the recombinant wild-type protein (WT) and the Cys18 to Ser (C18S) mutant. We find that the solubilities of the two proteins are similar. The kinetics of crystallization, however, are different. The WT crystallizes slowly enough for the metastable liquid-liquid coexistence to be easily observed. C18S, on the other hand, crystallizes rapidly; the metastable coexisting liquid phases of the pure mutant do not form. Nevertheless, the coexistence curve of C18S can be determined provided that crystallization is kinetically suppressed. In this way we found that the coexistence curve coincides with that of the WT. Despite the difference in the kinetics of crystallization, the two proteins were found to have the same crystal forms and almost identical X-ray structures. Our results demonstrate that even conservative point mutations can bring about dramatic changes in the kinetics of crystallization. The implications of our findings for cataract formation and protein crystallization are discussed.

A prospective study of sensitivity and specificity of adenosine deaminase estimation in the diagnosis of tuberculosis pleural effusion.

We prospectively evaluated the usefulness of adenosine deaminase [ADA] estimation in the diagnosis of tuberculosis [TB] pleural effusion. Seventy five subjects with pleural effusion were studied. Forty eight of them had TB pleural effusion [M:F: 37:11; mean age 33 +/- 14.4 years range 17-76] and the remaining 27 had pleural effusion due to causes other than TB [non-TB group] [M:F: 19:8; mean age 47.3 +/- 16.5 years; range 17-75]. Pleural fluid [PF] ADA levels were significantly higher in TB (n=48; mean 95.8 +/- 57.5 IU/L) compared with non-TB group (n=27; mean 30.7 +/- 27.2 IU/L) [p<0.001]. Serum ADA [S-ADA] levels were also significantly higher in TB (n=45; mean 39.6 +/- 18.3 IU/L) compared with non-TB group (n=26; mean 18.0 +/- 13.7 IU/L) [p<0.001]. PF-ADA levels were higher compared to S-SDA in TB (p <0.001) and non-TB groups [p<0.01]. Using a cut off of 35 IU/L, the sensitivity and specificity of PF-ADA in the diagnosis of TB was computed to be 83.3% and 66.6% respectively. At a cut-off level of 100 IU/L, PF-ADA was found to have a sensitivity 40% and specificity 100%. From this study it is concluded that, using 100 IU/L as the cut-off, it is possible to avoid pleural biopsy to ascertain the diagnosis of TB in as much as 40% of the patients.

Crystal cataracts: human genetic cataract caused by protein crystallization.

Several human genetic cataracts have been linked recently to point mutations in the gammaD crystallin gene. Here we provide a molecular basis for lens opacity in two genetic cataracts and suggest that the opacity occurs because of the spontaneous crystallization of the mutant proteins. Such crystallization of endogenous proteins leading to pathology is an unusual event. Measurements of the solubility curves of crystals of the Arg-58 to His and Arg-36 to Ser mutants of gammaD crystallin show that the mutations dramatically lower the solubility of the protein. Furthermore, the crystal nucleation rate of the mutants is enhanced considerably relative to that of the wild-type protein. It should be noted that, although there is a marked difference in phase behavior, there is no significant difference in protein conformation among the three proteins.