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Background: The reported accuracy of transbronchial needle aspiration (TBNA) for mediastinal staging in non-small cell lung cancer (NSCLC) varies widely. We performed a meta-analysis to estimate the accuracy of TBNA for mediastinal staging in NSCLC. Methods: Medline, Embase, and the bibliographies of retrieved articles were searched for studies evaluating TBNA accuracy with no language restriction. Meta-analytical methods were used to construct summary receiver-operating characteristic curves and to pool sensitivity and specificity. Results: Thirteen studies met inclusion criteria, including six studies that surgically confirmed all TBNA results and enrolled at least 10 patients with and without mediastinal metastasis (tier 1). Methodological quality varied but did not affect diagnostic accuracy. In tier 1 studies the median prevalence of mediastinal metastasis was 34%. Using a random effects model, the pooled sensitivity and specificity were 39% (95% Cl 17 to 61) and 99% (95% Cl 96 to 100), respectively. Compared with tier 1 studies, the median prevalence of mediastinal metastasis (81 %; p = 0.002) and pooled sensitivity (78%; 95% Cl 71 to 84; p = 0.009) were higher in non-tier 1 studies. Sensitivity analysis confirmed that the sensitivity of TBNA depends critically on the prevalence of mediastinal metastasis. The pooled major complication rate was 0.3% (95%Cl 0.01 to 4). Conclusions: When properly performed, TBNA is highly specific for identifying mediastinal metastasis in patients with NSCLC, but sensitivity depends critically on the study methods and patient population. In populations with a lower prevalence of mediastinal metastasis, the sensitivity of TBNA is much lower than reported in recent lung cancer guidelines. [ABSTRACT FROM AUTHOR]

Context: Focal pulmonary lesions are commonly encountered in clinical practice, and positron emission tomography (PET) with the glucose analog 18-fluorodeoxyglucose (FDG) may be an accurate test for identifying malignant lesions.Objective: To estimate the diagnostic accuracy of FDG-PET for malignant focal pulmonary lesions.Data Sources: Studies published between January 1966 and September 2000 in the MEDLINE and CANCERLIT databases; reference lists of identified studies; abstracts from recent conference proceedings; and direct contact with investigators.Study Selection: Studies that examined FDG-PET or FDG with a modified gamma camera in coincidence mode for diagnosis of focal pulmonary lesions; enrolled at least 10 participants with pulmonary nodules or masses, including at least 5 participants with malignant lesions; and presented sufficient data to permit calculation of sensitivity and specificity were included in the analysis.Data Extraction: Two reviewers independently assessed study quality and abstracted data regarding prevalence of malignancy and sensitivity and specificity of the imaging test. Disagreements were resolved by discussion.Data Synthesis: We used a meta-analytic method to construct summary receiver operating characteristic curves. Forty studies met inclusion criteria. Study methodological quality was fair. Sample sizes were small and blinding was often incomplete. For 1474 focal pulmonary lesions of any size, the maximum joint sensitivity and specificity (the upper left point on the receiver operating characteristic curve at which sensitivity and specificity are equal) of FDG-PET was 91.2% (95% confidence interval, 89.1%-92.9%). In current practice, FDG-PET operates at a point on the summary receiver operating characteristic curve that corresponds approximately to a sensitivity and specificity of 96.8% and 77.8%, respectively. There was no difference in diagnostic accuracy for pulmonary nodules compared with lesions of any size (P =.43), for semiquantitative methods of image interpretation compared with qualitative methods (P =.52), or for FDG-PET compared with FDG imaging with a modified gamma camera in coincidence mode (P =.19).Conclusions: Positron emission tomography with 18-fluorodeoxyglucose is an accurate noninvasive imaging test for diagnosis of pulmonary nodules and larger mass lesions, although few data exist for nodules smaller than 1 cm in diameter. In current practice, FDG-PET has high sensitivity and intermediate specificity for malignancy. [ABSTRACT FROM AUTHOR]

Background: Low-molecular-weight heparins may simplify the management of deep venous thrombosis. A critical clinical issue is whether this more convenient therapy is as safe and effective as treatment with unfractionated heparin.Purpose: To compare the safety and efficacy of low-molecular-weight heparins with those of unfractionated heparin for treatment of acute deep venous thrombosis.Data Sources: Reviewers identified studies by searching MEDLINE, reviewing references from retrieved articles, scanning abstracts from conference proceedings, and contacting investigators and pharmaceutical companies.Study Selection: Randomized, controlled trials that compared a low-molecular-weight heparin preparation with unfractionated heparin for treatment of acute deep venous thrombosis.Data Extraction: Two reviewers extracted data independently. Reviewers evaluated study quality using a validated four-item instrument.Data Synthesis: Eleven of 37 studies met inclusion criteria for three major outcomes. Most studies used proper randomization procedures, but only one was double-blinded. Compared with unfractionated heparin, low-molecular-weight heparins reduced mortality rates over 3 to 6 months of patient follow-up (odds ratio, 0.71 [95% CI, 0.53 to 0.94]; P = 0.02). For major bleeding complications, the odds ratio favored low-molecular-weight heparins (0.57 [CI, 0.33 to 0.99]; P = 0.047), but the absolute risk reduction was small and not statistically significant (0.61% [CI, -0.04% to 1.26%]; P = 0.07). For preventing thromboembolic recurrences, low-molecular-weight heparins seemed as effective as unfractionated heparin (odds ratio, 0.85 [CI, 0.63 to 1.14]; P > 0.2).Conclusions: Low-molecular-weight heparin treatment reduces mortality rates after acute deep venous thrombosis. These drugs seem to be as safe as unfractionated heparin with respect to major bleeding complications and appear to be as effective in preventing thromboembolic recurrences. [ABSTRACT FROM AUTHOR]

Background: Low-molecular-weight heparins are effective for treating venous thrombosis, but their cost-effectiveness has not been rigorously assessed.Objective: To evaluate the cost-effectiveness of low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis.Design: Decision model.Data Sources: Probabilities for clinical outcomes were obtained from a meta-analysis of randomized trials. Cost estimates were derived from Medicare reimbursement and other sources.Target Population: Two hypothetical cohorts of 60-year-old men with acute deep venous thrombosis.Time Horizon: Patient lifetime.Perspective: Societal.Intervention: Fixed-dose low-molecular-weight heparin or adjusted-dose unfractionated heparin.Outcome Measures: Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. An in-patient hospital setting was used for the base-case analysis. Secondary analyses examined outpatient treatment with low-molecular-weight heparin.Results Of Base-case Analysis: Total costs for inpatient treatment were $26,516 for low-molecular-weight heparin and $26,361 for unfractionated heparin. The cost of initial care was higher in patients who received low-molecular-weight heparin, but this was partly offset by reduced costs for early complications. Low-molecular-weight heparin treatment increased quality-adjusted life expectancy by approximately 0.02 years. The incremental cost-effectiveness of inpatient low-molecular-weight heparin treatment was $7820 per QALY gained. Treatment with low-molecular-weight heparin was cost saving when as few as 8% of patients were treated at home.Results Of Sensitivity Analysis: When late complications were assumed to occur 25% less frequently in patients who received unfractionated heparin, the incremental cost-effectiveness ratio increased to almost $75,000 per QALY gained. When late complications were assumed to occur 25% less frequently in patients who received low-molecular-weight heparin, this treatment resulted in a net cost savings. Inpatient low-molecular-weight heparin treatment became cost saving when its pharmacy cost was reduced by 31% or more, when it reduced the yearly incidence of late complications by at least 7%, when as few as 8% of patients were treated entirely as outpatients, or when at least 13% of patients were eligible for early discharge.Conclusions: Low-molecular-weight heparins are highly cost-effective for inpatient management of venous thrombosis. This treatment reduces costs when small numbers of patients are eligible for outpatient management. [ABSTRACT FROM AUTHOR]

Comments on an article concerning posttransplant lymphoproliferative disorder published in the November 1999 issue of the 'Chest' journal. Incidence of posttransplant lymphoproliferative disorder incidence in Epstein-Barr virus seroconverters.

A response by J-E. C. Holty and M. K. Gould to a letter to the editor about their article on the importance of complete mediastinal lymph node dissection after lung cancer resection is presented.

Comments on an article by Sanjay Saint and Michael A. Matthay which reviews the epidemiology and prevention of three common nosocomial complications of critical illness. Differences between narrative and systematic reviews; Key step in the direction of evidence-based critical care review; Failure of critical care practice in incorporating new scientific knowledge.

Objectives: Among lung cancer patients depression symptoms are common and impact outcomes. The aims of this study were to determine risk factors that contribute to persistent or new onset depression symptoms during lung cancer treatment, and examine interactions between depression symptoms and health domains that influence mortality., Materials and Methods: Prospective observational study in five healthcare systems and 15 Veterans Affairs medical centers. Patients in the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium with lung cancer were eligible. The 8-item Center for Epidemiologic Studies Depression (CES-D) scale was administered at baseline and follow-up. Scores ≥4 indicated elevated depressive symptoms. Health domains were measured using validated instruments. We applied logistic regression and Cox proportional hazards modeling to explore the association between depression symptoms, health domains, and mortality., Results: Of 1790 participants, 38% had depression symptoms at baseline and among those still alive, 31% at follow-up. Risk factors for depression symptoms at follow-up included younger age (OR=2.81), female sex (OR=1.59), low income (OR=1.45), not being married (OR=1.74) and current smoking status (OR=1.80); high school education was associated with reduced odds of depression symptoms at follow-up, compared with lesser educational attainment (OR=0.74) (all p values <0.05). Patients with depression symptoms had worse health-related quality of life, vitality, cancer-specific symptoms, and social support than patients without depression symptoms (all p<0.001). The association between depression symptoms and increased mortality is greater among patients with more lung cancer symptoms (p=0.008) or less social support (p=0.04)., Conclusions: Patient risk factors for depression symptoms at follow-up were identified and these subgroups should be targeted for enhanced surveillance. Patients with depression symptoms suffer across all health domains; however, only more lung cancer symptoms or less social support are associated with worse mortality among these patients. These potentially modifiable health domains suggest targets for possible intervention in future studies., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Multiple reports have described associations between occupational inhalant exposure and lung disease. Previous occupational lung disease investigations have studied populations consisting of both smokers and nonsmokers. Smoking complicates interpretation of toxicant exposure-response relationships. The objective of this study was to determine whether, among never-smokers, occupational exposure to gases, dusts, or fumes is associated with a history of respiratory disorders and pulmonary function test defined obstructive lung disease., Methods: We performed a retrospective analysis of 517 never-smoker patients who underwent pulmonary function testing in our clinical laboratory between 1986 and 1999. We calculated the relative risks of developing adverse respiratory health outcomes given a history of exposure to occupational inhalants., Results: Compared with persons with a negative occupational exposure history, exposed persons had an increased risk of reporting a history of bronchitis [relative risk (RR), 1.59; 95% confidence interval (CI), 1.20-2.12], recurrent lung infections (RR, 2.09; 95% CI, 1.14-3.82), and bronchodilator use (RR, 1.61; 95% CI, 1.26-2.06). There was also a statistically significant association between a history of inhalant exposure and the finding of an obstructive ventilatory defect on pulmonary function testing (RR, 1.79; 95% CI, 1.12-2.85). A history of inhalant exposure was not associated with self-reported asthma (RR, 1.08; 95% CI, 0.83-1.41). The population attributable risk estimates for respiratory disorders due to inhalant exposure were: bronchitis, 23.6%; recurrent lung infection, 36.3%; bronchodilator use, 24.3%; and obstructive lung disease, 29.6%., Conclusions: Occupational inhalant exposure is a strong risk factor for lung disease in this population of never smokers. A significant burden of respiratory disease in this population may be attributable to occupational inhalant exposure.

Inherited degenerating muscle diseases result in disintegration of muscle fibres, which is initiated by a lack of or alteration to a muscle protein. In Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) the protein is known to be dystrophin. The cellular function of dystrophin is not known in any detail but its absence appears to lead to a weakening of the sarcolemma. It has been proposed by Murphy and Kehrer that this leads ultimately to increased oxyradical production which may accelerate the degeneration. Studies have been carried out on individual muscle fibres derived from biopsy samples from patients with a number of degenerative muscle diseases. The glutathione cycling components, in particular glutathione and glutathione peroxidase, are significantly elevated in DMD, BMD and other diseases. Glutathione reductase is also elevated in some of these diseases. Energy producing systems are also affected particularly in intact fibres of muscle derived from muscle at an advanced stage of the disease. These results suggest that oxyradical damage may occur as a secondary consequence of muscle degenerating disease, leading to a breakdown in the glycogenolytic energy producing system.

These experiments examined the effects of N-ethylmaleimide on insulin- and oxidant-stimulated sugar transport in soleus muscle in terms of the Thiol-Redox model for insulin-stimulated adipocyte sugar transport (Czech, M.P. (1976) J. Cell. Physiol. 89, 661-668). Brief exposure (1 min) to N-ethylmaleimide (0.3-10 mM) inhibited the stimulatory effect of insulin (0.1 U/ml) on D-[U-14C]xylose uptake by rat soleus muscle. N-Ethylmaleimide also inhibited the stimulatory effects of H2O2 (5 mM), diamide (0.2 mM) and vitamin K-5 (0.05 mM). This effect of N-ethylmaleimide on insulin action was paralleled by the inhibition of 125I-labelled insulin binding by the muscle. N-ethylmaleimide lowered muscle ATP; however, its effects on sugar transport and 125I-labelled insulin binding could be dissociated from its effect on ATP. Exposing muscles to insulin prior to N-ethylmaleimide did not abolish the inhibitory effect of sulphydryl blockade on insulin-stimulated sugar transport, but did reduce the effect of the inhibitor by 20-30%. Conversely, when muscles were first allowed to bind 125I-labelled insulin and then exposed to the inhibitor, there was no effect of N-ethylmaleimide on pre-bound insulin. Exposure to diamide or vitamin K-5 before N-ethylmaleimide (1 mM) attenuated the inhibitory effect of sulphydryl blockade but no protective effect was observed with H2O2. None of the oxidants protected against the inhibitory effect of 3 mM N-ethylmaleimide. It is concluded that there are two N-ethylmaleimide-sensitive sites involved in the activation of muscle sugar transport at the post-receptor level. One of these would appear to be similar to the Thiol-Redox site described in the adipocyte; the other site appears to be an essential sulphydryl group whose function does not involve oxidation to a disulphide.

It has been reported that deactivation of insulin-stimulated sugar transport in adipocytes is an energy-dependent process (F. V. Vega, R. J. Key, J. E. Jordan, and T. Kono (1980) Arch. Biochem. Biophys. 203, 167-173). The stimulatory effect of insulin (0.1 U/ml) on the uptake of D-[U-14C]xylose by rat soleus muscle was rapidly reversed when muscle ATP was depleted by exposure to 2,4-dinitrophenol (0.5 mM). Insulin action was not completely eliminated by ATP depletion; there was a small, residual stimulatory effect of the hormone which persisted for about 30 min after muscle ATP had been lowered to an unmeasurable level. The extent of deactivation was not altered when the rate of ATP depletion was accelerated, either by increasing the 2,4-dinitrophenol concentration, or by inducing leakiness by incubating muscles for 90 min at 37 degrees C prior to the addition of the uncoupler. 2,4-Dinitrophenol lowered steady-state 125I-insulin binding. These differences between the effect of ATP depletion on insulin-stimulated sugar transport in muscle and adipose tissue may be related to the action of the uncoupler in lowering steady-state insulin binding in muscle. Such a fall in bound insulin could be expected to promote deactivation during the period of ATP depletion. However, at present the possibility that these differences may represent some more fundamental difference in deactivation between muscle and adipose tissue cannot be excluded.

1. These studies examined the theory that ATP served to regulate muscle sugar transport by a feedback mechanism. Xylose uptake by isolated rat soleus muscle was determined over a 5-min period following preincubation at 37 degrees C for various times in the presence of insulin (0.1 unit/ml), 2,4-dinitrophenol (0.5 or 0.05 mM) or salicylate (5 mM) or under anaerobic conditions. 2. Xylose uptake, measured in freshly isolated soleus muscles, was approximately 3.5--4.0 mumol/g per h. When the muscles were preincubated at 37 degrees C, this rate fell by 50% during the first 30 min and then slowly increased. 3. The stimulatory effect of insulin was evident within 2 min in freshly isolated soleus muscle and increased on preincubation, reaching a maximum value (approx. 14 mumol/g per h) after 20 min. 4. There was a 10-min lag period before xylose uptake was stimulated by anoxia. This lag period was approximately doubled when the incubation temperature was lowered from 37 degrees C. The stimulatory effect of anoxia was promptly reversed when muscles were transferred from anaerobic to aerobic conditions. 5. There was a 5-min lag period before xylose uptake was stimulated by 2,4-dinitrophenol (0.05 mM) or by sodium salicylate (mM). At a concentration of 0.5 mM, 2,4-dinitrophenol stimulated xylose uptake in freshly isolated muscle. Whereas the stimulatory effects of insulin, anoxia and salicylate all tended to plateau with time, the effect of 2,4-dinitrophenol tended to peak and then decline. 6. There was no obvious relationship between total muscle ATP levels and xylose uptake. The stimulatory effect of anoxia, 2,4-dinitrophenol or salicylate on xylose uptake was not preceded by the fall in muscle ATP. Similarly, ATP levels did not change when xylose uptake was stimulated by anoxia at 27 degrees C, or when xylose uptake was restored to basal values by transferring muscles from anaerobic to aerobic conditions. 7. It was argued that the presence of the myofibrils could act as a permeability barrier, which would limit the access of ATP produced within the interior of the cell to a regulatory site on, or close to, the sarcolemma. On the other hand, it is conceivable that the ATP produced on the periphery of the fibre by the subsarcolemmal mitochondria could play a more specific role in the feedback regulation of sugar transport. 8. Insulin stimulated xylose uptake in the presence of 2,4-dinitrophenol (0.5 mM) when this was measured in freshly isolated muscle, but not after a period of preincubation. This suggested that there may be some ATP-dependent process involved in the stimulatory effect of insulin.

A new technique for isolating fragmented plasma membranes from skeletal muscle has been developed that is based on gentle mechanical disruption of selected homogenate fractions. (Na+ + K+)-stimulated, Mg2+-dependent ATPase was used as an enzymatic marker for the plasma membrane, Ca2+-stimulated, Mg2+-dependent ATPase as a marker for sarcoplasmic reticulum, and succinate dehydrogenase for mitochondria. Cell segments in an amber low-speed (800 x g) pellet of a frog muscle homogenate were disrupted by repeated gentle shearing with a Polytron homogenizer. Sarcoplasmic reticulum was released into the low-speed supernatant, whereas most of the plasma membrane marker remained in a white, fluffy layer of the sediment, which contained sarcolemma and myofibrils. Additional gentle shearing of the white low-speed sediment extracted plasma membranes in a form that required centrifugation at 100,000 x g for pelleting. This pellet, the fragmented plasma membrane fraction, had a relatively high specific activity of (Na+ + K+)-stimulated ATPase compared with the other fractions, but it had essentially no Ca2+-stimulated ATPase activity and only a small percentage of the succinate dehydrogenase activity of the homogenate. Experimental evidence suggests that the fragmented plasma membrane fraction is derived from delicate transverse tubules rather than from the thicker, basement membrane-coated sarcolemmal sheath of muscle cells. Electron microscopy showed small vesicles lined bu a single thin membrane. Hydroxyproline, a characteristic constituent of collagen and basememt membrane, could not be detected in this fraction.

The uptake of D-[U-14C]xylose by isolated rat soleus muscle was studied, using D-[1-3H]-sorbitol as an extracellular marker. Xylose uptake was limited by the diffusion of the sugar into and through the extracellular water. This could be overcome in part by allowing the test sugars to pre-equilibrate in the extracellular water at 0 degrees C, before measuring xylose uptake. It was not necessary to fill the extracellular water with the test sugars to obtain maximum rates of xylose uptake. From this it was concluded that the sugar carrier sites were located in a specific region on the plasma membrane, readily accessible to sugar carrier sites were located in a specific region on the plasma membrane, readily accessible to sugars entering the interstitial water. Pre-equilibration was more effective in the absence of insulin than in the presence of the hormone. This suggested that insulin may influence sugar uptake at some site prior to the cell membrane. Pre-incubation at 0 degrees C itself stimulated sugar transport. This effect of cooling was not influenced by insulin, nor did it appear to affect the stimulatory action of insulin on xylose transport.

Muscle ATP levels were lowered by incubating rat soleus muscles under anaerobic conditions, or in the presence of 2:4-dinitrophenol (0.5 mM), EDTA (5 mM) or mannitol (400 mM). 125I-insulin binding, measured under equilibrium conditions at 25 degrees C, was reduced by 49-71% in ATP-depleted muscles. Insulin binding was also determined using two other procedures which minimized internalization of 125I-insulin: these were (a) 5 min at 25 degrees C, and (b) 24 h at 3 degrees C. Under these conditions, 125I-insulin binding was reduced by 28-55% in ATP-depleted muscles. These results confirm that in soleus muscle the effect of ATP-depletion on 125I-insulin binding is actually concerned with the binding step itself and not merely a reflection of ATP-dependent internalization of the bound hormone.