Evaluating the Use of CT-Derived Lung Volumes in Donor-Recipient Lung Size Matching for Lung Transplantation in Patients With Interstitial Lung Disease and/or Idiopathic Pulmonary Fibrosis.

PURPOSE: This study aims to assess the efficacy of current measurement strategies for lung sizing and the feasibility of future use of computed tomography (CT)-derived lung volumes to predict a donor-recipient lung size match during bilateral lung transplants. METHODS: We reviewed the data of 62 patients who underwent bilateral lung transplantation for interstitial lung disease and/or idiopathic pulmonary fibrosis from 2018 to 2019. Data for recipients was retrieved from the department's transplant database and medical records, and the donor's data was retrieved from the DonorNet. The data included demographic data, lung heights, measured total lung capacity (TLC) from plethysmography for recipients and estimated TLC for donors, clinical data, and CT-derived lung volumes in both pre- and post-transplant recipients. The post-transplant CT-derived lung volume in recipients was used as a surrogate for donor lung CT volumes due to inadequate or poor donor CT data. Computed tomography-derived lung volumes were calculated using thresholding, region growing, and cutting techniques on Computer-Aided Design and Mimics (Materialise NV, Leuven, Belgium) programs. Preoperative CT-derived lung volumes in recipients were compared with the plethysmography TLC, Frustum Model, and donor-predicted TLC. The ratio of the recipient's pre-and postoperative CT-derived volumes, the ratio of preoperative CT-derived lung volume, and donor-estimated TLC were studied to detect a correlation with 1-year outcomes. RESULTS: The recipient preoperative CT-derived volume correlated with the recipient preoperative plethysmography TLC (Pearson correlation coefficient [PCC] of 0.688) and with the recipient Frustum model volume (PCC of 0.593). The recipient postoperative CT-derived volume correlated with the recipient's postoperative plethysmography TLC (PCC of 0.651). There was no statistically significant correlation between recipients' CT-derived pre- or postoperative volume with donor-estimated TLC. The ratio of preoperative CT-derived volume to donor-estimated TLC correlated inversely with the length of ventilation (P value = .0031). The ratio of postoperative CT-derived volume to preoperative CT-derived volume correlated inversely with delayed sternal closure (P = .0039). No statistically significant correlations were found in evaluating outcomes related to lung oversizing in the recipient (defined as a postoperative to preoperative CT-derived lung volume ratio of >1.2). CONCLUSIONS: Generating CT-derived lung volumes is a valid and convenient method for evaluating lung volumes for transplantation in patients with ILD and/or IPF. Donor-estimated TLC should be interpreted carefully. Further studies should derive donor lung volumes from CT scans for a more accurate evaluation of lung size matching.

Characteristics and Outcomes Among Patients With Early Venous Thromboembolic Events After Lung Transplant.

BACKGROUND: Despite several previous studies reporting a high frequency of venous thromboembolism (VTE) after lung transplant (LT), few actionable risk factors have been identified. There are limited data regarding the practice patterns of anticoagulation use among patients with LT. METHODS: All adult patients with single or bilateral LT between 2012 and 2016 were included (n = 324; mean age, 56.3 ± 13.3 years; male, 61.1%). Demographic, clinical, and laboratory variables before and after LT were recorded. Follow-up data included survival up to 3 years post-transplant. Development of VTE during the first 30 days after LT was the primary outcome variable. RESULTS: The overall incidence of VTE during the first 30 days after LT was 29.9% (n = 97), among which the majority were upper extremity thromboses. Female sex, personal history of VTE, hospitalization at the time of transplant, and use of 3 or more central venous catheters during index hospitalization were independently associated with VTE. The use of anticoagulants was independently associated with a reduced risk of VTE. Despite increased morbidity, the development of VTE was not associated with worse post-transplant survival. CONCLUSIONS: A significant proportion of patients develop early VTE after LT. Limiting the number of central catheters to < 3 during the post-transplant period, along with the early institution of thromboprophylaxis, may lower the risk of VTE.

Iontophoretic skin delivery systems: Success and failures.

Iontophoretic transdermal delivery uses a small electric current to push charged molecules into the skin under an electrode of same polarity and offers an attractive option to facilitate the delivery of macromolecules or hydrophilic molecules and to improve patient compliance. This technique has been used in physical therapy clinics for several decades, though the science was not always there to support claims of clinical effectiveness. Recently, this modality of treatment has undergone more systematic and rigorous investigations to withstand the scrutiny of regulatory authorities. In recent years various drugs have gained FDA approval for iontophoretic patches. This technique is gaining recognition due to better compliance rates, non-invasive drug delivery leading to fewer side effects, and sustained release of the drug. Furthermore, programmed delivery and bolus delivery systems have helped with customizing the drug dosage and frequency of dosage based on the patient's need.

Microneedle-mediated intradermal delivery of epigallocatechin-3-gallate.

OBJECTIVE: Epigallocatechin-3-gallate (EGCG) is the physiologically most active and abundant flavanol, accounting for 50-80% of green tea catechins. It is an anti-inflammatory, antioxidant, chemopreventive and skin photoprotective agent. However, light sensitivity and low permeability of EGCG across the stratum corneum due to its high molecular weight as well as strong binding to the lipid bilayers in the skin make it difficult to be used as a key ingredient in cosmetic products. This study aimed to formulate a photostable hydrogel of EGCG with good rheological properties for dermal application and investigate the effect of skin microporation using maltose microneedles on its permeation through dermatomed porcine skin. METHODS: Effect of l-glutathione on photodegradation of EGCG was investigated by exposing samples to ultraviolet irradiation for 1 h using a solar simulator. Hydrogels with varying concentrations of Carbopol 980 (0.5-2% w/v) as an gelling agent were prepared, and their rheological properties were evaluated using a rheometer. Skin microporation was confirmed by assessing the skin resistance, transepidermal water loss and calcein imaging of the microchannels created by the microneedles. Permeation of EGCG from aqueous solution as well as the rheologically optimized hydrogel through the dermatomed porcine skin (untreated and microneedle treated) was evaluated using static vertical Franz diffusion cells. RESULTS: l-glutathione acting as a co-antioxidant and photostabilizer significantly (P < 0.05) reduced the degradation of EGCG from 21.53 ± 2.78% to 1.0 ± 0.68% after 1 h of ultraviolet irradiation. Rotational and oscillatory rheological tests indicated that the hydrogel containing 1.5% Carbopol 980 is acceptable for topical application in terms of flow behaviour, elasticity, spreadability, structural stability and thixotropy. Microneedle-treated skin showed significant enhancement (P < 0.05) in the delivery of EGCG to viable epidermis and dermis from the aqueous solution (38.67 ± 2.96 µg cm(-2) ) as well as hydrogel (24.60 ± 2.62 µg cm(-2) ) in comparison with the untreated skin (24.16 ± 2.11 and 15.62 ± 0.24 µg cm(-2) for aqueous solution and hydrogel, respectively). CONCLUSION: Addition of glutathione in EGCG formulations significantly reduces its photodegradation. Skin microporation with maltose microneedles facilitates the penetration of EGCG across the stratum corneum into the deeper skin layers - viable epidermis and dermis.

Formulation of tocopherol nanocarriers and in vitro delivery into human skin.

OBJECTIVE: Tocopherol is stronger antioxidant than tocopherol acetate but due to its viscous form, poor water solubility, instability to light and skin irritation issues it is not used in the current marketed formulations. To overcome the drawbacks, tocopherol was formulated as nanostructured lipid carriers and nanoemulsion. The objective of the study was to formulate tocopherol as nanocarriers. METHOD: Nanostructured lipid carriers (NLCs) and nanoemulsion (NE) were prepared by homogenization technique. They were characterized for particle size and zeta potential. In vitro release study was performed using dialysis method, and skin permeation was carried out using human cadaver skin. Further, antioxidant activity was tested by ferric reducing antioxidant potential (FRAP) assay and skin irritation testing was performed on Epiderm skin model. Effect of UV degradation was studied using solar simulator. RESULTS: The size and zeta potential of NLC was 67.0 nm ± 1.2 and -32.0 mV ± 1.2, whereas for NE, it was 586.5 nm ± 209.6 and -10 mV ± 0.6. In vitro release study showed that 30% of tocopherol was released from NLC in the first 2 h of the study as compared to only 4% from NE. Permeation study from human skin showed that 762.3 ng mL(-1) ± 184.6 of tocopherol was delivered into the epidermis when formulated as NLCs as compared to 182.3 ng mL(-1) ± 52.7 from NE. FRAP assay was performed to test the antioxidant activity of formulated tocopherol, and it was seen that both formulations were able to retain the antioxidant activity. Skin irritation testing showed that NLC was non-irritant to the skin. NLC and NE were also able to protect tocopherol from UV degradation. CONCLUSION: Based on the studies conducted, it can be concluded that formulating tocopherol as NLCs is beneficial to produce a stable, non-irritant and aqueous formulation.

Stable insulin-secreting ducts formed by reprogramming of cells in the liver using a three-gene cocktail and a PPAR agonist.

With the long-term aim of developing a new type of therapy for diabetes, we have investigated the reprogramming of liver cells in normal mice toward a pancreatic phenotype using the gene combination Pdx1, Ngn3, MafA. CD1 mice were rendered diabetic with streptozotocin and given a single dose of Ad-PNM, an adenoviral vector containing all three genes. Ad-PNM induced hepatocytes of the liver to produce insulin, and the blood glucose became normalized. But over several weeks, the insulin-positive cells were lost and the blood glucose rose back to diabetic levels. Simultaneous administration of a peroxisome-proliferator-activated receptor agonist, WY14643, caused remission of diabetes at a lower dose of Ad-PNM and also caused the appearance of a population of insulin-secreting ductal structures in the liver. The insulin-positive ducts were stable and were able to relieve diabetes in the long term. We show that the effect of WY14643 is associated with the promotion of cell division of the ductal cells, which may increase their susceptibility to being reprogrammed toward a beta cell fate.

Predictors of requirement of mechanical ventilation in patients with chronic obstructive pulmonary disease with acute respiratory failure.

BACKGROUND AND OBJECTIVE: Acute exacerbation of chronic obstructive pulmonary disease (COPD) leads to increased morbidity, mortality and requirement of invasive mechanical ventilation (MV). The aim of this study was to identify predictors of need of MV in these patients. MATERIALS AND METHODS: Clinical symptomatology, demographic profile, biochemical parameters including renal functions, liver functions and acid base parameters, and acute physiology and chronic health evaluation II (APACHE II) score at the time of admission were recorded in 100 patients of COPD exacerbation. Various parameters were compared between patients in whom MV was required with those managed with medical therapy. RESULTS: MV was required in 73% of the patients. Parameters found to be independent predictors of need of MV were: Admission APACHE-II score ≥ 11.5 {adjusted odds ratio (OR) [95% confidence interval (CI)]: 1.42 [1.08-1.86]; P = 0.012}, first day pH ≤ 7.28 (adjusted OR [95% CI]: 1.09 [1.02-1.15]; P = 0.008), first day PaCO2 ≥ 68.6 mmHg (adjusted OR [95% CI]: 1.09 [1.02-1.15]; P = 0.004) and worse premorbid functional status (adjusted OR [95% CI]: 17.01 [1.95-148.68]; P = 0.01). CONCLUSIONS: Underlying disease severity as assessed by premorbid functional status and APACHE-II score, and the acuity of respiratory system decompensation as assessed by the admitting arterial pH and PaCO2, are independent predictors of need of MV in patients with exacerbation of COPD.

Quantification of skin penetration of antioxidants of varying lipophilicity.

Antioxidants play a vital role in protecting the skin from environmental distress. As the skin is constantly exposed to harmful UV radiation, endogenous antioxidants present in the superficial layers of the skin neutralize reactive oxygen species. Over time, antioxidants become depleted and loss their protective effect on the skin. Therefore, supplementing skin with topical antioxidant can help replenish this loss and fight the oxidative stress. The objective of this study was to deliver antioxidants topically and quantify the amount permeated in the stratum corneum and underlying skin. Polyphenols (catechin, resveratrol and curcumin) and vitamin (retinol) with various lipophilic properties were delivered via porcine ear skin, using propylene glycol as a vehicle. The amount in the stratum corneum and underlying skin was quantified using tape stripping and skin extraction methods, respectively, and samples were analysed via HPLC. All four antioxidants permeated into the skin from the propylene glycol vehicle. The order of the amount of antioxidant in the stratum corneum was catechin > resveratrol~ retinol> curcumin, whereas that in the underlying skin was retinol > catechin~ resveratrol~ curcumin. Of the total amount of polyphenols in the skin, approximately 90% was retained in the stratum corneum whereas 10% was quantified in the underlying skin. In contrast, 10% of retinol was retained in the stratum corneum whereas 90% permeated in the underlying skin. Polyphenols (catechin, resveratrol and curcumin) showed high concentration in the stratum corneum whereas retinol showed high accumulation in the underlying layers of the skin.

Subcutaneous concentrations following topical iontophoretic delivery of diclofenac.

A self-contained Wearable Electronic Disposable Drug Delivery (WEDD(®)) patch was used to demonstrate that diclofenac levels delivered by iontophoresis are greater than estimated minimal effective concentrations in local subcutaneous tissue and are also greater than either passive transdermal or intravenous delivery using hairless rats. In vitro iontophoretic delivery was evaluated to optimize donor cell formulation using Franz diffusion cells and 1000 NMWL Millipore ultrafiltration membrane. In vivo animal studies were done using patches powered with a 4-volt system, consisting of a 1-volt Zn anode and Ag/AgCl cathode with built in 3-volt lithium battery. Blood and microdialysis samples were collected at different time points after patch application. Current levels increased to 1.0 mA at 30 min, then fell to a steady state of ~ 0.4 mA. Both WEDD(®) and passive patches produced measurable levels of diclofenac in the subcutaneous tissue below the application site (C(max) ± SE = 113.3 ± 61.7 ng/mL and 36.3 ± 15.9 ng/mL, respectively). The dose delivered in six hours was calculated to be 0.226 ± 0.072 mg and 0.430 ± 0.048 mg in passive and iontophoretic delivery, respectively. Diclofenac was not detected in the subcutaneous tissue after intravenous administration of 1.5 mg/kg diclofenac solution. The trend indicates that WEDD(®) can be used to successfully deliver diclofenac to subcutaneous tissue to concentrations higher when compared to either passive delivery or intravenous dosing of 1.5 mg/kg.

In vitro and in vivo iontophoretic transdermal delivery of an anti-parkinsonian agent.

To objective of this work was to study the feasibility of iontophoretic delivery of SLV 318 (7-(4-benzyl-1-piperazinyl)-2(3H)-benzoxazolone methanesulfonate) across hairless rat skin in vitro and in vivo. The effect of counter-ions and temperature were investigated for optimizing SLV 318 solubility. The effect of electrode efficiency and total current applied on the delivery of SLV 318 were studied using Franz diffusion cells and samples were analyzed using HPLC. Delivery increased with increasing concentration. For current-time combinations, electrode had to be replaced every 9h. Passive, iontophoretic (0.1 mA/cm(2) for 1h) and intravenous studies were performed in vivo. Blood samples collected were analyzed using LC-MS/MS. SLV 318 had higher solubility with NaCl (75 mM) as a counter-ion at 25°C than with other counter-ions tested. In vivo iontophoresis significantly enhanced the permeation and also reduced its lag time (P<0.05). The C(max) of SLV 318 during 1h iontophoresis was 6.56 ± 0.68 ng/mL at 1.31 ± 0.29 h (T(max)) as compared to 2.96 ± 0.29 ng/mL at 25.32 ± 0.67 h (T(max)) by 24h passive permeation. The in vitro and in vivo data has shown the feasibility to enhance delivery of SLV 318 by iontophoresis.

In vitro transdermal iontophoretic delivery of penbutolol sulfate.

Iontophoretic transport of penbutolol sulfate across porcine ear skin was studied. Passive transdermal flux of the drug in phosphate-buffered saline was 7.65 microg/cm(2) hr. There was statistically significant flux enhancement when direct current iontophoresis was applied. Iontophoresis (0.11 mA/cm(2), 0.17 mA/cm(2), and 0.22 mA/cm(2)) for 6 hr, resulted in net transport of 87.36 microg/cm(2), 137.51 microg/cm(2), and 201.12 microg/cm(2) of penbutolol sulfate, respectively. After 24 hr, cumulative amount of penbutolol transported were 201.63, 300.76, and 359.98 microg/cm(2), respectively. There was a 2.20- (0.11 mA/cm(2)), 3.26- (0.17 m/Acm(2)), and 4.28-fold (0.22 mA/cm(2)) enhancement in transcutaneous steady-state flux values compared to passive delivery. Steady-state fluxes of penbutolol sulfate also increased proportionally to current density. Steady-state fluxes calculated from the linear portion of the cumulative amount versus time curves for penbutolol sulfate were 16.68, 24.97, and 32.76 microg/cm(2)/hr at current densities of 0.11, 0.17, and 0.22 mA/cm(2). This study provides initial evidence for the potential use of iontophoresis for enhanced transdermal delivery of penbutolol sulfate.

Enhanced transdermal delivery of low molecular weight heparin by barrier perturbation.

The purpose of this work was to investigate the in vitro transdermal delivery of low molecular weight heparin (LMWH). Hairless rat skin was mounted on Franz diffusion cells and treated with various enhancement strategies. Passive flux was essentially zero and remained low even after iontophoresis (0.065 U cm(-2) h(-1)) or application of ultrasound (0.058 U cm(-2) h(-1)). A significant increase in flux across tape stripped skin (4.0 U cm(-2) h(-1)) suggests the interaction of stratum corneum (SC) with LMWH which was confirmed using Differential Scanning Calorimetry and Fourier Transform-Infrared spectrophotometry. Maltose microneedles were then employed as a means to locally disrupt and bypass the SC. Transepidermal water loss (TEWL) and transcutaneous electrical resistance (TER) were measured to confirm the barrier disruption. Microneedles breached the SC resulting in increased TEWL, decreased TER and enhanced LMWH permeability (0.175 U cm(-2) h(-1)). Microneedles when used in conjunction with iontophoresis had a synergistic effect on LMWH delivery resulting in enhancement of flux by 14.7-fold as compared to iontophoresis used alone. Confocal laser scanning microscopy substantiated the evidence about LMWH interaction with SC. In conclusion, LMWH was shown to interact with SC and therefore tape stripping or microneedles dramatically increased its delivery due to disruption of the SC skin barrier.

Enhancement of transdermal delivery of heparin by various physical and chemical enhancement techniques.

Conventional anticoagulants such as unfractionated heparin and warfarin have numerous limitations compared with low-molecular-weight heparin (LMWH). However, the need for repetitive parenteral administration is still a major disadvantage of LMWH, and the absorption of macromolecules such as LMWH across the gastrointestinal tract is very poor. Due to these problems with oral delivery of LMWH, transdermal delivery can be considered as an alternate route of administration. However, overcoming the skin barrier is necessary for the transport of larger molecules across the stratum corneum. This review focuses on the transdermal delivery of LMWH, providing a brief overview of heparin delivery via invasive and oral routes and discusses the advantages of using LMWH rather than heparin for transdermal delivery, and the primary reasons for poor permeability of LMWH. Various strategies employed for transdermal delivery of heparin are summarized, and chemical and physical enhancement techniques or suitable formulations that can be used to improve transcutaneous penetration and various chemical enhancers that act on the skin by different modes of action are discussed. We also consider physical approaches such as iontophoresis, electroporation, and ultrasound, as well as combination strategies to deliver heparin. The developments in physical and chemical enhancement strategies over the past decade are summarized. In addition, recent novel approaches such as microneedles employed for the transdermal delivery of LMWH are also discussed.

Thermal and non-thermal methods to evaluate compatibility of granisetron hydrochloride with tablet excipients.

Compatibility of granisetron hydrochloride with selected excipients was assessed using Differential Scanning Calorimetry (DSC) as a thermal screening technique. Non-thermal methods like Fourier Transform Infrared spectroscopy and Thin Layer Chromatography were used as complementary techniques to adequately support and assist in interpretation of DSC results. Some drug-excipient interaction was observed with beta-cyclodextrin, 2-hydroxypropyl-beta-cyclodextrin, mannitol, and magnesium stearate in DSC studies. However, further evaluation of these incompatible excipients with non-thermal methods showed that these excipients were compatible with granisetron hydrochloride. Non-thermal methods were, thus, of help in interpreting DSC results and excluding all relevant pharmaceutical incompatibilities.

Validation of the modified Berlin questionnaire to identify patients at risk for the obstructive sleep apnoea syndrome.

BACKGROUND & OBJECTIVES: Awareness regarding obstructive sleep apnoea (OSA) among general public as well as practicing physicians is low in India. The present study was undertaken to test the utility of modified Berlin questionnaire for risk categorization of OSA in Indian setting. METHODS: The modified Berlin questionnaire was administered in 180 middle aged adults (of 320 screened), of whom, 104 underwent overnight polysomnograhy, in a cross-sectional study at a tertiary care, referral center in north India. Questionnaire addressed the presence of frequency of snoring, wake time sleepiness, fatigue, obesity and hypertension. Subjects with persistent and frequent symptoms in any two of these three domains were considered in high risk category for obstructive sleep apnoea. Overnight polysomnograhy was performed to measure apnoea and hypopnoea index (AHI). RESULTS: Questions about the symptoms demonstrated internal consistency (Cronbach alpha correlations 0.92-0.96). Of the 180 respondents to the screening questions, 80 were in the high risk and the rest were in low risk group. For 104 subjects who underwent polysomnograhy, risk grouping was useful in prediction of AHI. High risk category predicted an AHI >5 with a sensitivity of 86 per cent, specificity of 95 per cent, positive and negative predictive values of 96 and 82 per cent respectively. These results were comparable to Berlin questionnaire study done in the western population for validation. INTERPRETATION & CONCLUSION: On the basis of the findings of present study it is concluded that administration of modified Berlin questionnaire prior to a polysomnography study can identify high risk subjects and can thus avoid unnecessary polysomnography studies especially in resource-limited settings. To identify subjects at risk for OSA syndrome in general population, this questionnaire can be applied. However, the findings of the present study need to be confirmed further in a large number of subjects in a community-based setting.

Predictors of development and outcome in patients with acute respiratory distress syndrome due to tuberculosis.

OBJECTIVE: To study the predictors of development and determinants of outcome in patients with acute respiratory distress syndrome (ARDS) due to tuberculosis (TB). METHODS: Retrospective case-control study of demographic, clinical and laboratory data of hospitalised adult patients with active TB. RESULTS: Of 2733 TB patients treated during 1980-2003, 29 (1.06%; 1.21 patients/year; mean age 31.6 +/- 10.9 years; 16 males) developed ARDS (cases). Seven had pulmonary TB and 22 had miliary TB (MTB); 298 (mean age 32.0 +/- 14.2 years; 110 males) who did not develop ARDS constituted controls. Presence of MTB (OR 4.6, 95%CI 1.2-17.8; P = 0.02), duration of illness beyond 30 days at presentation (OR 177.9, 95%CI 39-811.7; P < 0.001), absolute lymphocyte count < 1625/ mm3 (OR 4.5, 95%CI 1.1-19.3; P = 0.04) and serum ALT > 100 IU (OR 15.7, 95%CI 3.0-81.1, P < 0.001) were independent predictors of ARDS development. Twelve cases died (41.4%). Patients with APACHE II score >18; those with APACHE II score <18 in the presence of hyponatraemia and PaO2/FIO2 ratio <108.5 were likely to die. CONCLUSIONS: In patients with TB, prolonged illness, MTB, absolute lymphocytopaenia and elevated ALT are independently associated with ARDS development. APACHE II score, serum sodium and PaO2/FIO2 ratio are determinants of outcome.

A stepped approach for prediction of obstructive sleep apnea in overtly asymptomatic obese subjects: a hospital based study.

BACKGROUND AND PURPOSE: Prevalence of obstructive sleep apnea (OSA) is high in obese subjects, many of whom may not be overtly symptomatic. Polysomnography (PSG) is a costly and time-consuming investigation. Since it is not feasible to subject all obese individuals to PSG, it is useful to define predictors of OSA among these subjects. PATIENTS AND METHODS: One hundred and eighteen obese subjects [body mass index (BMI)> or =25 kg/m(2)] presenting to the hospital with non-sleep related complaints were included, of which 53 subjects with PSG evidence of OSA [apnea-hypopnea index (AHI)> or =15/h] were defined as cases and 65 subjects without any evidence of OSA (AHI<15/h) were defined as controls. Anthropometry, biochemical investigations, blood gas analysis, pulmonary function tests, and PSG were performed for all subjects. RESULTS: Waist hip ratio (WHR) (as percentage of a standard) [odds ratio (95% CI): 1.07 (1.00-1.14); P = 0.049] male gender [odds ratio (95% CI): 3.97 (0.99-15.81); P = 0.046] and neck circumference (NC) [odds ratio (95% CI): 1.23 (1.03-1.47); P = 0.023] were found to be independent predictors of OSA. Overnight oxygen desaturation data were evaluated in patients selected as having OSA on the basis of these clinical markers, and the best cut-off for level of desaturation (10%) was defined. The stepped approach had a specificity, sensitivity, positive and negative predictive value of 89.2, 88.5, 86.8 and 90.6%, respectively, for the diagnosis of OSA. CONCLUSIONS: Male gender, WHR and NC are independent predictors of OSA in overtly asymptomatic obese subjects. A stepped approach to diagnose OSA should be used, as it is accurate and cost-effective.

Wegener's granulomatosis: an isolated lung mass responding to antituberculosis therapy and atypical course.

We describe an unusual case of Wegener's granulomatosis (WG), in a middle aged, non-smoking female who presented with a lung mass with constitutional symptoms. FNABC from mass revealed a single ill-defined granuloma without necrosis. There was a definite clinical and radiological response to anti-tuberculosis treatment. She was later found to have another mass lesion in nasopharynx. ANCA was negative initially but became positive once disease flare up occurred. Multisystem involvement with clinical features of vasculitis were seen during the flare up and resulted in a fatal outcome. Unusual features and literature on this entity is discussed.