Coronary artery calcification is associated with mortality independent of pulmonary embolism severity: a retrospective cohort study.

AIM: To assess coronary artery calcification (CAC) and vascular calcification in patients with pulmonary embolism (PE) and correlate this with mortality. MATERIALS AND METHODS: PE severity was quantified using computed tomography pulmonary angiography (CTPA) in 400 consecutive cases using the modified Miller score (1-5, mild; 6-11, moderate; 12-16, severe). Right ventricle strain was assessed using the right/left ventricle diameter (RV/LV) ratio. CAC score (CACS) was assessed using a four-point scale (CACS mild 1-3, moderate 4-8, severe 9-12) for each vessel and summed to give the total CACS. Follow-up for mortality was obtained at 3 years. RESULTS: PE severity was classified as mild in 48%, moderate in 21%, and severe in 32% of cases. The median modified Miller score was 6 (Interquartile range [IQR] 2, 14) and median total CACS was 2 (IQR 0, 7). All-cause mortality occurred in 128 (32%) patients. Patients with CAC were three times more likely to die than patients without CAC (Hazard ratio [HR] 2.96; 95% CI 1.84, 4.77; p<0.001), and patients with severe CAC were at the highest risk (HR 4.62; 95% CI 2.73, 7.83, p<0.001). Gender, modified Miller score and RV/LV ratio were not predictive of mortality. In multivariate analysis both CACS and age were independent predictors of 3-year all-cause mortality. Of the patients with CAC who died, the presence of coronary artery disease was only documented in 34 (32%). CONCLUSION: CACS is an independent predictor of all-cause mortality in patients with PE, and has important implications for subsequent patient management.

Breast arterial calcification on mammography and risk of coronary artery disease: a SCOT-HEART sub-study.

AIM: To assess the prevalence of breast arterial calcification (BAC) in patients who also underwent routine surveillance mammography, and to determine the association with cardiovascular risk factors, coronary artery calcification, and coronary artery disease on coronary computed tomography angiography (CCTA). MATERIALS AND METHODS: Four hundred and five female participants were identified who had undergone CCTA and subsequent mammography in the SCOT-HEART randomised controlled trial of CCTA in patients with suspected stable angina. Mammograms were assessed visually for the presence and severity of BAC. RESULTS: BAC was identified in 93 (23%) patients. Patients with BAC were slightly older (63±7 versus 59±8 years, p<0.001), with a higher cardiovascular risk score (19±11 versus 16±10, p=0.022) and were more likely to be non-smokers (73% versus 49%, p<0.001). In patients with BAC, coronary artery calcification was present in 58 patients (62%; relative risk [RR] 1.26, 95% confidence intervals [CI]: 1.04, 1.53; p=0.02), non-obstructive coronary artery disease in 58 (62%; RR 1.27, 95% CI: 1.04 to 1.54, p=0.02), and obstructive coronary artery disease in 19 (20%; RR 1.62, 95% CI: 0.98, 2.66; p=0.058). Patients without BAC were very unlikely to have severe coronary artery calcification (negative predictive value 95%) but the diagnostic accuracy of BAC to identify coronary artery disease was poor (AUC 0.547). CONCLUSION: Although BAC is associated with the presence and severity of coronary artery calcification, the diagnostic accuracy to identify patients with coronary artery disease or obstructive coronary artery disease is poor.

Display colour scale effects on diagnostic performance and reader agreement in cardiac CT and prostate apparent diffusion coefficient assessment.

AIM: To investigate the effect of colour scale choice on diagnostic performance in the interpretation of medical images. MATERIALS AND METHODS: Twelve clinicians interpreted 210 myocardial computed tomography (CT) perfusion (CTP) examinations, and nine clinicians interpreted 165 magnetic resonance imaging (MRI) apparent diffusion coefficient (ADC) prostate images. In three separate sessions, each participant read the same image set using greyscale, hot-iron, and rainbow scales, respectively. Participants scored their level of confidence for tumour presence in the ADC study, and for ischaemia in the CTP study, from 0 to 100. The area under the receiver operating characteristic (ROC) curve (AUC) was used as the performance metric. For cases that scored >50, CTP readers' agreement on the ischaemic transmural extent was analysed, and ADC map readers' selected values and coordinates for the lowest ADC within the detected tumour were compared across different colour scales. RESULTS: For CTP detection, the AUC was up to 0.10 higher with greyscale, 0.67±0.02 (standard error), compared to rainbow, 0.56±0.02, and detection with hot-iron was in between (0.61±0.03). For ischaemic transmural lesion categorisation, observed inter-reader agreement was highest with greyscale for category 25-50%. There is a small tendency for rainbow and greyscale to outperform hot-iron in the detection of prostate tumours. The selected lowest ADC value and pixel localisation was similar with all colour scales. CONCLUSIONS: The present findings suggest that colour visualisation has a measurable effect on CTP and ADC performance. Further investigation is necessary to determine the magnitude of the effect in diagnostic tasks.

Multimodality quantitative assessments of myocardial perfusion using dynamic contrast enhanced magnetic resonance and 15O-labelled water positron emission tomography imaging.

Kinetic modelling of myocardial perfusion imaging data allows the absolute quantification of myocardial blood flow (MBF) and can improve the diagnosis and clinical assessment of coronary artery disease (CAD). Positron emission tomography (PET) imaging is considered the reference standard technique for absolute quantification, whilst oxygen-15 (15O)-water has been extensively implemented for MBF quantification. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) has also been used for MBF quantification and showed comparable diagnostic performance against (15O)-water PET studies. We investigated for the first time the diagnostic performance of two different PET MBF analysis softwares PMOD and Carimas, for obstructive CAD detection against invasive clinical standard methods in 20 patients with known or suspected CAD. Fermi and distributed parameter modelling-derived MBF quantification from DCE-MRI was also compared against (15O)-water PET, in a subgroup of 6 patients. The sensitivity and specificity for PMOD was significantly superior for obstructive CAD detection in both per vessel (0.83, 0.90) and per patient (0.86, 0.75) analysis, against Carimas (0.75, 0.65), (0.81, 0.70), respectively. We showed strong, significant correlations between MR and PET MBF quantifications (r=0.83-0.92). However, DP and PMOD analysis demonstrated comparable and higher haemodynamic differences between obstructive versus (no, minor or non)-obstructive CAD, against Fermi and Carimas analysis. Our MR method assessments against the optimum PET reference standard technique for perfusion analysis showed promising results in per segment level and can support further multi-modality assessments in larger patient cohorts. Further MR against PET assessments may help to determine their comparative diagnostic performance for obstructive CAD detection.

Genotyping and comparative pathology of Spirocerca in black-backed jackals (Canis mesomelas) in South Africa.

BACKGROUND: The pathology of spirocercosis, a disease caused by the infestation of carnivores with the nematode Spirocerca lupi, has been extensively described in domestic dogs and coyotes. However, it has not been described in wild carnivores in South Africa. The aim of this study was to evaluate whether black-backed jackals are a host for Spirocerca species and to provide a detailed description of the associated pathology. Jackals were also stratified according to age and the Spirocerca species recovered were characterized using molecular techniques. METHODS: Standard necropsies were performed on routinely culled jackals from three of the nine provinces of South Africa during the period June 2012 to February 2013. Jackals were screened for the presence of pathognomonic Spirocerca-induced lesions and for evidence of aberrant migration. Relevant samples were submitted for histopathology and collected larvae were genotyped at nine microsatellite loci. RESULTS: Spirocerca lupi-associated aortic lesions were found in 16 of 93 (17%) black-backed jackals. Of these, four (25%) were associated with S. lupi larvae. Genotyping of the larvae revealed amplification of all nine loci that amplified dog-derived S. lupi, with the same level of polymorphism in the allele size ranges. Only 1 of 93 jackals had an esophageal nodule with concurrent S. lupi-induced aortic aneurysms. The single esophageal nodule found did not contain adult nematodes, nor did it communicate with the esophageal lumen. None of the jackals that were examined had macroscopically evident spondylitis, which is frequently reported in the dog. Histopathology of the S. lupi-induced aortic lesions in the jackal revealed replacement of elastic and smooth muscle fibers by fibrous connective tissue. In cases where inflammation was present, the inflammatory infiltrate consisted predominantly of eosinophils. The single esophageal nodule histologically resembled the early inflammatory nodule described in dogs and consisted of fibrous connective tissue, multifocal accumulation of lymphocytes, plasma cells and rare hemosiderin-laden macrophages. CONCLUSIONS: These lesions suggest that the life cycle of S. lupi may not or only rarely be completed in jackals. A possible explanation might be that jackals are relatively resistant to developing significant pathology associated with S. lupi-infection. However, before any conclusions can be drawn, many more jackals, including those that die naturally will have to be investigated for evidence of S. lupi infection.

CT myocardial perfusion imaging: current status and future directions.

Computed tomography (CT) imaging of the heart has advanced rapidly, and it is now possible to perform a comprehensive assessment at a low radiation dose. CT myocardial perfusion imaging can provide additive information to CT coronary angiography, and is particularly useful in patients with heavily calcified coronary arteries or coronary artery stents. A number of protocols are now available for CT myocardial perfusion including static, dynamic, and dual-energy techniques. This review will discuss the current status of CT myocardial perfusion imaging, its clinical application, and future directions for this technology.

Cardiovascular PET-CT imaging: a new frontier?

Cardiovascular positron-emission tomography combined with computed tomography (PET-CT) has recently emerged as an imaging technology with the potential to simultaneously describe both anatomical structures and physiological processes in vivo. The scope for clinical application of this technique is vast, but to date this promise has not been realised. Nonetheless, significant research activity is underway to explore these possibilities and it is likely that the knowledge gained will have important diagnostic and therapeutic implications in due course. This review provides a brief overview of the current state of cardiovascular PET-CT and the likely direction of future developments.

Iterative reconstruction and individualized automatic tube current selection reduce radiation dose while maintaining image quality in 320-multidetector computed tomography coronary angiography.

AIM: To assess the effect of two iterative reconstruction algorithms (AIDR and AIDR3D) and individualized automatic tube current selection on radiation dose and image quality in computed tomography coronary angiography (CTCA). MATERIALS AND METHODS: In a single-centre cohort study, 942 patients underwent electrocardiogram-gated CTCA using a 320-multidetector CT system. Images from group 1 (n = 228) were reconstructed with a filtered back projection algorithm (Quantum Denoising Software, QDS+). Iterative reconstruction was used for group 2 (AIDR, n = 379) and group 3 (AIDR3D, n = 335). Tube current was selected based on body mass index (BMI) for groups 1 and 2, and selected automatically based on scout image attenuation for group 3. Subjective image quality was graded on a four-point scale (1 = excellent, 4 = non-diagnostic). RESULTS: There were no differences in age (p = 0.975), body mass index (p = 0.435), or heart rate (p = 0.746) between the groups. Image quality improved with iterative reconstruction and automatic tube current selection [1.3 (95% confidence intervals (CI): 1.2-1.4), 1.2 (1.1-1.2) and 1.1 (1-1.2) respectively; p < 0.001] and radiation dose decreased [274 (260-290), 242 (230-253) and 168 (156-180) mGy cm, respectively; p < 0.001]. CONCLUSION: The application of the latest iterative reconstruction algorithm and individualized automatic tube current selection can substantially reduce radiation dose whilst improving image quality in CTCA.

Aortic stenosis, atherosclerosis, and skeletal bone: is there a common link with calcification and inflammation?

AIMS: The pathophysiology of aortic stenosis shares many similarities with atherosclerosis and skeletal bone formation. Using non-invasive imaging, we compared aortic valve calcification and inflammation activity with that measured in atherosclerosis and bone. METHODS AND RESULTS: Positron emission and computed tomography was performed using 18F-sodium fluoride (18F-NaF, calcification) and 18F-fluorodeoxyglucose (18F-FDG, inflammation) in 101 patients with calcific aortic valve disease (81 aortic stenosis and 20 aortic sclerosis). Calcium scores and positron emission tomography tracer activity (tissue-to-background ratio; TBR) were measured in the aortic valve, coronary arteries, thoracic aorta, and bone. Over 90% of the cohort had coexistent calcific atheroma, yet correlations between calcium scores were weak or absent (valve vs. aorta r(2) = 0.015, P = 0.222; valve vs. coronaries r(2) = 0.039, P = 0.049) as were associations between calcium scores and bone mineral density (BMD vs. valve r(2) = 0.000, P = 0.766; vs. aorta r(2) = 0.052, P = 0.025; vs. coronaries r(2) = 0.016, P = 0.210). 18F-NaF activity in the valve was 28% higher than in the aorta (TBR: 2.66 ± 0.84 vs. 2.11 ± 0.31, respectively, P < 0.001) and correlated more strongly with the severity of aortic stenosis (r(2) = 0.419, P < 0.001) than 18F-NaF activity outwith the valve (valve vs. aorta r(2) = 0.167, P < 0.001; valve vs. coronary arteries r(2) = 0.174, P < 0.001; valve vs. bone r(2) = 0.001, P = 0.806). In contrast, 18F-FDG activity was lower in the aortic valve than the aortic atheroma (TBR: 1.56 ± 0.21 vs. 1.81 ± 0.24, respectively, P < 0.001) and more closely associated with uptake outwith the valve (valve vs. aorta r(2) = 0.327, P < 0.001). CONCLUSION: In patients with aortic stenosis, disease activity appears to be determined by local calcific processes within the valve that are distinct from atherosclerosis and skeletal bone metabolism.

Cardiac and coronary CT comprehensive imaging approach in the assessment of coronary heart disease.

Cardiac CT is a rapidly advancing technology. Non-invasive CT coronary angiography is an established technique for assessing coronary heart disease with accuracy similar to invasive coronary angiography. CT myocardial perfusion imaging can now identify perfusion defects in animal models and humans. MRI is the current 'gold standard' for the assessment of myocardial viability, but it is now also possible to assess delayed enhancement by CT. This has led to the possibility of a 'one-stop shop' for cardiovascular imaging that would provide information on anatomy, function, perfusion and viability in one rapid diagnostic test at a radiation dose equivalent to contemporary nuclear medicine imaging. This review discusses the current status of 'one-stop shop' cardiac CT assessment, clinical utility and directions for future research.

Proposed histological progression of the Spirocerca lupi-induced oesophageal lesion in dogs.

This study aims to outline the histological progression of the Spirocerca lupi nodule from infection to neoplastic transformation. Sixty-two spirocercosis-induced nodules, 42 non-neoplastic and 20 neoplastic, were stained with HE. Ten non-overlapping high power fields per nodule were examined and non-neoplastic and neoplastic nodules were compared. Inflammation was scored 0-3 and revealed a score of 1.91+/-0.52 in the non-neoplastic and 0.97+/-0.5 in the neoplastic cases (p<0.01). In most non-neoplastic cases the inflammatory infiltrate was lymphoplasmacytic and in the neoplastic cases neutrophils predominated. Necrosis was scored 0-3 and revealed a score of 0.88+/-0.41 in the non-neoplastic and 1.47+/-0.5 in the neoplastic cases (p<0.01). The average number of mitoses over 10 high power fields per nodule was 1.31+/-1.55 in the non-neoplastic compared to 42.85+/-30.79 in the neoplastic cases (p<0.01). The average number of multinucleated giant cells over 10 high power fields per nodule was 0.9+/-1.45 in the non-neoplastic compared to 13.9+/-14.66 in the neoplastic cases (p<0.01). In the non-neoplastic cases, collagen, immature fibroblasts and fibroblast activation (excessively plump euchromatic nuclei with single or multiple prominent nucleoli) were scored 0-3 and a combined score, fibroblasts+activation score-collagen was calculated. The non-neoplastic cases were divided into a combined score of 1 (n=27). The 2 groups had similar scores for inflammation and necrosis, but were significantly different (p<0.01) in mitotic index (0.26+/-0.46 vs. 1.89+/-1.65) and number of multinucleated cells (0 vs. 1.4+/-1.6). These results indicate 2 stages in the non-neoplastic nodules: early inflammation, characterized by fibrocytes and abundant collagen, and a pre-neoplastic stage, characterized by activated fibroblasts and reduced collagen.

The pathology of tuberculosis caused by Mycobacterium tuberculosis in a herd of semi-free-ranging springbok (Antidorcas marsupialis).

The first detailed description of the pathology of tuberculosis, caused by Mycobacterium tuberculosis, in springbok is reported. The springbok were part of a semi-free-ranging herd kept on the grounds of iThemba Laboratory for Accelerator Based Science (LABS) in the Kuils River district of the Western Cape Province, South Africa. Mycobacterium tuberculosis was isolated from three animals out of a total of 33 sampled, with two animals showing tuberculosis lesions. The index case was an adult ewe that showed advanced miliary tuberculosis with marked macroscopic and microscopic lesions in the lungs, pleura and respiratory lymph nodes, and numerous acid-fast bacilli. Six healthy rams were sampled nine months later and a pilot study indicated miliary tuberculosis lesions in one ram, which again were macroscopically most prominent in the lungs, pleura and respiratory lymph nodes. Macroscopic lesions were also noted in the sternal, iliac, prefemoral and retropharyngeal lymph nodes. Microscopy in this animal revealed lesions in the macroscopically affected organs as well as numerous other lymph nodes, and suspected lesions occurred in the testicle and colon. Acid-fast bacilli were scarce to moderate in affected organs. Because of the miliary nature of the lesions in both affected animals, the route of infection could not be established conclusively. The lesions in most affected organs of both animals resembled classical tuberculous granulomas. A main study conducted on healthy animals 19 months after the pilot study failed to find any animal with tuberculosis lesions in the group of 25 sampled, and all were negative for mycobacteria via mycobacterial culture.

The FEMA GRAS assessment of aromatic substituted secondary alcohols, ketones, and related esters used as flavor ingredients.

This publication is the 11th in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of intended use. The list of GRAS substances has now grown to more than 2100 substances. Elements that are fundamental to the safety evaluation of flavor ingredients include exposure, structural analogy, metabolism, pharmacokinetics and toxicology. Flavor ingredients are evaluated individually and in the context of the available scientific information on the group of structurally related substances. In this monograph, a detailed interpretation is presented on the renal carcinogenic potential of the aromatic secondary alcohol alpha-methylbenzyl alcohol, aromatic ketone benzophenone, and corresponding alcohol benzhydrol. The relevance of these effects to the flavor use of these substances is also discussed. The group of aromatic substituted secondary alcohols, ketones, and related esters was reaffirmed as GRAS (GRASr) based, in part, on their rapid absorption, metabolic detoxication, and excretion in humans and other animals; their low level of flavor use; the wide margins of safety between the conservative estimates of intake and the no-observed-adverse effect levels determined from subchronic and chronic studies and the lack of significant genotoxic and mutagenic potential.

Chronic vanadium poisoning in calves and its treatment with calcium disodium ethylenediaminetetraacetate.

Sixteen Friesland heifer calves aged between 96 and 157 days were removed from a dairy farm that had been polluted with vanadium and randomly allocated into two equal groups (n = 8). The objective of the trial was to determine whether calcium disodium ethylenediaminetetraacetate (CaNa(2)EDTA) could be used as a treatment for cattle running in environments high in background vanadium. The treatment group received 80 mg CaNa(2)EDTA per kg body weight intraperitonealy (i.p.) twice a week over a 10-week period. The control group received normal saline i.p. over the same period. During the trial calves were exposed to a daily intake of vanadium in the form of contaminated tef hay derived from the farm of origin. In addition, the total mixed ration was spiked with a further 20 mg V(2)O(5)/kg feed to compensate for possible on-farm inhalation exposure. A stochastic model was used to estimate daily intake of vanadium as a distribution function. The model estimated that the daily intake of vanadium varied between an absolute minimum of 33 mg/day to an absolute maximum of 124 mg/day. The average intake of vanadium was 71.8 mg per day per calf. Various chemical pathology parameters were measured throughout the trial as well as urine excretion rates of vanadium and lymphocyte stimulation counts. All calves were slaughtered and necropsied in cohorts of 4-6 animals at monthly intervals after completion of the trial and withdrawal of vanadium from the ration. Tissue concentrations of vanadium were determined and necropsy findings were noted. The study found that CaNa(2)EDTA appears to enhance the excretion of vanadium in calves, but could not prove that the treatment had a protective effect against vanadium exposure. Calves were able to tolerate the prolonged treatment with CaNa(2)EDTA without side-effects.

Cryptococcus neoformans granuloma in the lung and spinal cord of a free-ranging cheetah (Acinonyx jubatus). A clinical report and literature review.

A 6-year-old, male, wild-born, free-ranging cheetah (Acinonyx jubatus) was evaluated for acute onset of progressive lameness in the right hind limb. Survey radiographs were unrewarding and myelography indicated an intramedullary compressive mass at the L3-L4 region. A fine needle aspirate of the lesion indicated the presence of Cryptococcus organisms. Necropsy confirmed the presence of granulomas (cryptococcoma) in the lung and the spinal cord (meningomyelitis) caused by Cryptococcus neoformans var. gattii. Cryptococcus neoformans is a yeast-like organism that is a potential pathogen to many species. Initial infection is thought to be of respiratory origin and then it commonly disseminates systemically from the nasal cavity or lungs to the skin, eyes and central nervous system in particular. The cheetah tested negative for both feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV), as have all the previously reported cheetah cases. C. neoformans is a non-contagious, opportunistic organism and is the most common systemic mycoses in domestic cats and the cheetah.

Investigating the palliative efficacy of whole-brain radiotherapy for patients with multiple-brain metastases and poor prognostic features.

AIMS: Trials have shown that patients with multiple-brain metastases and poor prognostic features have a short median survival after whole-brain radiotherapy (WBRT). Quality of life (QoL) and other parameters to assess the palliative efficacy of WBRT have not previously been studied in this group of patients. We therefore attempted to do this. MATERIALS AND METHODS: We performed three studies between 1997 and 2001. The two later studies were designed according to the results from the preceding study. Each of them revealed the difficulties in studying this group of unwell patients with a short survival. RESULTS: Thirty-eight patients were studied. They had at least two of three poor prognostic features, such as Karnofsky performance status (KPS) < 70, over 60 years of age, and primary other than breast cancer. The overall median survival was 8 weeks (95% CI 6-10). Twenty-four patients had a KPS < 70 and a median survival of 6 weeks (95% CI 4-9). At 8 weeks after WBRT, 14 out of 15 surviving patients for whom data were obtained suffered deterioration in QoL scores, Barthel or KPS. Ten of the 38 patients (26%, 95% CI 13-43%) improved in at least one of these parameters during the assessment period. Only three out of 38 patients discontinued steroids after the radiotherapy. Side-effects of WBRT were common. All patients experienced alopecia and lethargy after radiotherapy. CONCLUSIONS: Further trials involving larger numbers of patients are necessary. These studies offer further information on the limited response rates to WBRT, side-effects and effects on QoL, which need to be discussed with patients before they accept or decline the offer of cranial irradiation.

Investigation of the dependence of inferred interfacial tension on rotation rate in a spinning drop tensiometer.

The spinning drop tensiometer is widely used to study the interfacial properties of many systems. However, there have also been several reported limitations with the spinning drop tensiometer. In this paper, it is shown that there is a relationship between the measured interfacial tension and the rotation rate of the drop. A detailed investigation of this relationship is presented.

Dynamics of low-energy helium vapor pulses.

We report results of experiments in which pulses of helium vapor are produced by a current pulse in a chromium film covered with superfluid helium at around 0.3 K. The pulses were detected by a titanium bolometer operating at 0.47 K. The shape of the detected signal is a strong function of the power of the initiating current pulse. For low powers the signal from a single current pulse also contains a single peak, but for higher powers, a single current pulse produces two and then at the highest powers, three peak signals. To analyze the origin of these phenomena we report results of hybrid gas-dynamics and hydrodynamics simulations, which demonstrate that the signals arise from shock waves formed in the vapor. The shock waves form due to the presence of a gradient in the small ambient background of helium vapor in the chamber and are extremely sensitive to the pulse power.

Bone marrow-derived cells as progenitors of lung alveolar epithelium.

We assessed the capacity of plastic-adherent cultured bone marrow cells to serve as precursors of differentiated parenchymal cells of the lung. By intravenously delivering lacZ-labeled cells into wild-type recipient mice after bleomycin-induced lung injury, we detected marrow-derived cells engrafted in recipient lung parenchyma as cells with the morphological and molecular phenotype of type I pneumocytes of the alveolar epithelium. At no time after marrow cell injection, did we detect any engraftment as type II pneumocytes. In addition, we found that cultured and fresh aspirates of bone marrow cells can express the type I pneumocyte markers, T1alpha and aquaporin-5. These observations challenge the current belief that adult alveolar type I epithelial cells invariably arise from local precursor cells and raise the possibility of using injected marrow-derived cells for therapy of lung diseases characterized by extensive alveolar damage.