A seventeenth-centuryMycobacterium tuberculosisgenome supports a Neolithic emergence of theMycobacterium tuberculosiscomplex

BACKGROUND: Although tuberculosis accounts for the highest mortality from a bacterial infection on a global scale, questions persist regarding its origin. One hypothesis based on modern Mycobacterium tuberculosis complex (MTBC) genomes suggests their most recent common ancestor followed human migrations out of Africa approximately 70,000 years before present. However, studies using ancient genomes as calibration points have yielded much younger dates of less than 6000 years. Here, we aim to address this discrepancy through the analysis of the highest-coverage and highest-quality ancient MTBC genome available to date, reconstructed from a calcified lung nodule of Bishop Peder Winstrup of Lund (b. 1605-d. 1679). RESULTS: A metagenomic approach for taxonomic classification of whole DNA content permitted the identification of abundant DNA belonging to the human host and the MTBC, with few non-TB bacterial taxa comprising the background. Genomic enrichment enabled the reconstruction of a 141-fold coverage M. tuberculosis genome. In utilizing this high-quality, high-coverage seventeenth-century genome as a calibration point for dating the MTBC, we employed multiple Bayesian tree models, including birth-death models, which allowed us to model pathogen population dynamics and data sampling strategies more realistically than those based on the coalescent. CONCLUSIONS: The results of our metagenomic analysis demonstrate the unique preservation environment calcified nodules provide for DNA. Importantly, we estimate a most recent common ancestor date for the MTBC of between 2190 and 4501 before present and for Lineage 4 of between 929 and 2084 before present using multiple models, confirming a Neolithic emergence for the MTBC

Minimal guidewire length for central venous catheterization of the right subclavian vein : A CT-based consecutive case series

BACKGROUND: Central venous catheter (CVC) misplacement occurs frequently after right subclavian vein catheterization. It can be avoided by using ultrasound to confirm correct guidewire tip position in the lower superior vena cava prior to CVC insertion. However, retraction of the guidewire during the CVC insertion may dislocate the guidewire tip from its desired and confirmed position, thereby resulting in CVC misplacement. The aim of this study was to determine the minimal guidewire length required to maintain correct guidewire tip position in the lower superior vena cava throughout an ultrasound-guided CVC placement in the right subclavian vein.METHODS: One hundred adult patients with a computed tomography scan of the chest were included. By using multiplanar reconstructions from thin-sliced images, the distance from the most plausible distal puncture site of the right subclavian vein to the optimal guidewire tip position in the lower superior vena cava was measured (vessel length). In addition, measurements of equipment in common commercial over-the-wire percutaneous 15-16 cm CVC kits were performed. The 95th percentile of the vessel length was used to calculate the required minimal guidewire length for each CVC kit.RESULTS: The 95th percentile of the vessel length was 153 mm. When compared to the calculated minimal guidewire length, the guidewires were up to 108 mm too short in eight of eleven CVC kits.CONCLUSION: After confirmation of a correct guidewire position, retraction of the guidewire tip above the junction of the brachiocephalic veins should be avoided prior to CVC insertion in order to preclude dislocation of the catheter tip towards the right internal jugular vein or the left subclavian vein. This study shows that many commercial over-the-wire percutaneous 15-16 cm CVC kits contain guidewires that are too short for right subclavian vein catheterization, i.e., guidewire retraction is needed prior to CVC insertion

Ventilation/perfusion SPECT in chronic obstructive pulmonary disease: an evaluation by reference to symptoms, spirometric lung function and emphysema, as assessed with HRCT.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation which is not fully reversible. Despite the heterogeneity of COPD, its diagnosis and staging is currently based solely on forced expiratory volume in 1 s (FEV(1)). FEV(1) does not explain the underlying pathophysiology of airflow limitation. The relationship between FEV(1), symptoms and emphysema extent is weak. Better diagnostic tools are needed to define COPD. Tomographic lung scintigraphy [ventilation/perfusion single photon emission tomography (V/P SPECT)] visualizes regional V and P. In COPD, relations between V/P SPECT, spirometry, high-resolution computed tomography (HRCT) and symptoms have been insufficiently studied. The aim of this study was to investigate how lung function imaging and obstructive disease grading undertaken using V/P SPECT correlate with symptoms, spirometric lung function and degree of emphysema assessed with HRCT in patients with COPD. METHODS: Thirty patients with stable COPD were evaluated with the Medical Research Council dyspnoea questionnaire (MRC) and the clinical COPD questionnaire (CCQ). Spirometry was performed. The extent of emphysema was assessed using HRCT. V/P SPECT was used to assess V/P patterns, total reduction in lung function and degree of obstructive disease. RESULTS: The total reduction in lung function and degree of obstructive disease, assessed with V/P SPECT, significantly correlated with emphysema extent (r = 0.66-0.69, p < 0.0001) and spirometric lung function (r = 0.62-0.74, p < 0.0005). The correlation between emphysema extent and spirometric lung function was weaker. No correlation between MRC, CCQ and objective measurements was found. CONCLUSION: V/P SPECT is sensitive to early changes in COPD. V/P SPECT also has the possibility to identify comorbid disease. V/P SPECT findings show a significant correlation with emphysema extent and spirometric lung function. We therefore recommend that scintigraphic signs of COPD, whenever found, should be reported. V/P SPECT can also be used to categorize the severity of functional changes in COPD as mild, moderate or severe

Pharmacological normalization of circulation after acute brain death.

BACKGROUND: Circulatory instability is a serious problem after brain death in organ donors. The hypotension is often counteracted with infusion of large amounts of crystalloid solutions, which may impair lung function leading to rejection of the lungs as donor organs. The aim was to show that the circulation can be normalized pharmacologically for 24 h in pigs after total removal of the brain and brainstem by decapitation (between C2 and C3). METHODS: Twenty-four 40-kg pigs (n = 8 × 3) were included: non-decapitated, decapitated, and decapitated with pharmacological treatment. All animals got the same basal fluid supply and ventilation. The pharmacological treatment consisted of the neuronal monoamine reuptake blocker cocaine and low doses of noradrenaline and adrenaline. Desmopressin, triiodothyroxine, thyroxine and cortisol were also given. RESULTS: After decapitation, a catecholamine storm occurred, with an increase of noradrenaline and adrenaline by a factor of 79 and 298, respectively. Thirty minutes later, the pigs were hypotensive. The median time to the aortic pressure that was less than 40 mmHg was 9:09 h (range 5:50 to 22:01). After 6 h, the concentration of thyroid hormones and cortisol was significantly reduced. With pharmacological treatment of decapitated animals, the aortic pressure, renal blood flow, creatinine, urine production, liver function and blood gases did not differ significantly from the non-decapitated control animals. CONCLUSION: Pharmacological substitution of pituitary gland function, blockade of peripheral catecholamine neuronal reuptake and low doses of catecholamines normalize circulation in decapitated pigs throughout a 24-h observation period, whereas untreated decapitated pigs all develop severe circulatory collapse within 12 h

Inflammation and chronic colonization of Haemophilus influenzae in sputum in COPD patients related to the degree of emphysema and bronchiectasis in high-resolution computed tomography

The presence of bacteria in the lower airways in COPD results in inflammation, further airway structural damage, and might lead to repeated exacerbations. We have previously shown that chronic colonization of Haemophilus influenzae during stable disease is related to increased inflammation, and we now aimed to relate previous findings of bacterial colonization and inflammation to the degree of radiological findings of bronchiectasis and emphysema. Thirty-nine patients with COPD were included in their stable state, and a high-resolution computed tomography of the lung was performed. They were followed-up monthly for up to a maximum of 6 months or until exacerbation, and they answered questionnaires, performed spirometry, and induced sputum at every visit. Thirty-five patients had emphysema with an emphysema degree of median 20% (interquartile range 10-50), and five patients had bronchiectasis, of which only four could expectorate sputum. The degree of emphysema correlated with several inflammatory mediators in sputum, such as interleukin-8 concentration, myeloperoxidase activity, and Leukotriene B4 concentration. Ten patients were chronically colonized with H. influenzae (ie, had a positive culture for H. influenzae at all visits). The four sputum patients with bronchiectasis were chronically colonized with H. influenzae and showed higher degree of H. influenzae growth compared to patients without bronchiectasis. During exacerbation, there was no longer any correlation between emphysema degree and inflammation, but patients with bronchiectasis showed higher sputum purulence score than patients without bronchiectasis. Emphysema and bronchiectasis in COPD patients show different clinical features. The presence of emphysema is more related to inflammation, while bronchiectasis is associated with bacterial colonization. We believe that both emphysema and bronchiectasis are therefore COPD phenotypes of highest impact and need evaluation to prevent further disease progression

Airway resistance and reactance are affected in systemic sclerosis.

Interstitial lung disease often occurs as an early complication of systemic sclerosis (SSc). The aim was to investigate whether impulse oscillometry (IOS) could be used to evaluate lung impairment in SSc

Pulmonary blood volume indexed to lung volume is reduced in newly diagnosed systemic sclerosis compared to normals - a prospective clinical cardiovascular magnetic resonance study addressing pulmonary vascular changes

Background: Pulmonary involvement, manifested as pulmonary arterial hypertension or pulmonary fibrosis, is the most common cause of death in systemic sclerosis (SSc). We aimed to explore the feasibility of detecting early pulmonary involvement in SSc using recently developed non-invasive quantitative measures of pulmonary physiology using cardiovascular magnetic resonance (CMR). Methods: Twenty-seven SSc patients (9 men, 57 +/- 13 years) and 10 healthy controls (3 men, 54 +/- 9 years) underwent CMR to determine the pulmonary blood volume (PBV) and the PBV variation (PBVV) throughout the cardiac cycle. Patients underwent Doppler echocardiography, high-resolution computed tomography (HRCT), and pulmonary function testing by spirometry. Comparisons were performed using the unpaired t-test and linear regression analysis was performed with Pearson's correlation coefficient (r). Results: Compared to healthy controls, the PBV indexed to lung volume (PBVI) was lower in patients (16 +/- 4 vs 20 +/- 5%, p < 0.05). There was no difference in PBV (466 +/- 87 vs 471 +/- 122 mL, p = 0.91) or PBVV/stroke volume (45 +/- 10 vs 40 +/- 6%, p = 0.09). There were no significant correlations between PBVI and pulmonary artery pressure estimated by Doppler (p = 0.08) the lung's diffusion capacity for carbon monoxide (DLCO) (p = 0.09), vital capacity (p = 0.45), or pulmonary fibrosis by HRCT (p = 0.74). Conclusions: This study is the first to measure the PBV in humans using CMR. Compared to healthy controls, newly diagnosed SSc patients have a reduced amount of blood in the pulmonary vasculature (PBVI) but unchanged pulmonary vascular distensibility (PBVV/stroke volume). PBVI is unrelated to DLCO, pulmonary artery pressure, vital capacity, and the presence of pulmonary fibrosis. PBVI may be a novel parameter reflecting vascular lung involvement in early-stage SSc, and these findings may be consistent with pathophysiological changes of the pulmonary vasculature