HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Akira, M. Articles by Morinaga, K. Search for Related Content PubMed PubMed Citation Articles by Akira, M. Articles by Morinaga, K. Social Bookmarking                      What's this? Hotlight (NEW!) What's Hotlight?

Inhalational Talc Pneumoconiosis: Radiographic and CT Findings in 14 Patients

¹ Department of Radiology, Kinki-Chuo Chest Medical Center, 1180 Nagasone-cho, Sakai City, Osaka 591-8555, Japan.
² Department of Pathology, Kinki-Chuo Chest Medical Center, Osaka 591-8555, Japan.
³ Department of Internal Medicine, Kinki-Chuo Chest Medical Center, Osaka 591-8555, Japan.
⁴ Department of Environmental Health, National Institute of Industrial Health, Kawasaki 214-8585, Japan.

Received May 23, 2005; accepted after revision August 9, 2005.

 
Address correspondence to M. Akira.

Abstract

Top Abstract Introduction Materials and Methods Results Discussion References

 
OBJECTIVE. The purpose of this study was to evaluate the radiographic and CT findings of inhalational talc pneumoconiosis.

CONCLUSION. Large opacities of talc pneumoconiosis progress more often than do small opacities. The CT findings of talc pneumoconiosis overlap those of silicosis and asbestosis.

Keywords: chest • high-resolution CT • lung • pneumoconiosis • radiography • talc • thin-section CT

Introduction

Top Abstract Introduction Materials and Methods Results Discussion References

 
Thorel [1] reported the first case of talc pneumoconiosis in 1896. Since then talc has been recognized as a cause of pneumoconiosis in miners, millers, rubber workers, and other occupational groups [2]. Talc is pure hydrous magnesium silicate with an ideal chemical composition of 63.5% SiO₂, 31.7% MgO, and 4.8% H₂O, but in practice substitutions of ions occur in the mineral lattice or the talc is contaminated by other minerals [3]. The chest radiographic manifestations of talc pneumoconiosis have been well described [4-8]. The CT features of talcosis due to IV administration of talc have been reported [9-11]. To our knowledge, however, the CT features of talc pneumoconiosis due to occupational talc exposure have not been well described [12, 13]. We present the radiographic and CT manifestations and serial changes on chest radiographs of 14 patients with pathologically proved talc pneumoconiosis.

Materials and Methods

Top Abstract Introduction Materials and Methods Results Discussion References

 
Patients
The study included 14 patients with pathologically proved talc pneumoconiosis consecutively admitted to our hospital between 1973 and 1998. The diagnosis was based on clinical history, occupational exposure to talc dust, and histologic findings obtained at transbronchial lung biopsy (n =8) or autopsy (n = 6). A thoracic pathologist reviewed the pathologic specimens. The pathologic findings of talc pneumoconiosis included diffuse interstitial fibrosis, ill-defined fibrotic nodules, and foreign body granulomas associated with dense accumulations of birefringent talc dust particles [1, 3]. All patients were men. The mean age was 59 years (range, 40-71 years) at initial evaluation. Mean duration of exposure to talc dust was 19 years (range, 8-35 years). Eight patients worked in a talc factory. Four patients were exposed to talc dust used in the manufacture of rubber products. One patient was exposed to talc dust used as an additive in a cosmetics factory, and one to talc dust used as an additive in a confectionery. Eleven patients ceased work after the initial evaluation. Ten patients were smokers, and four never smoked. Smokers had a smoking history ranging from 18 to 69 pack-years (mean, 36.3 pack-years).

The patients underwent follow-up chest radiography. Serial radiographs were available for all patients during a mean follow-up period of 16 years (range, 6-25 years). All patients underwent one or more CT examinations between 1988 and 2004. Chest radiographs obtained within 1 week of CT were available for all patients. After 6-25 years of follow-up, four patients had died of respiratory failure, one patient had died of myocardial infarction, and one had died of cerebral infarction. The postmortem lungs from one patient were inflated, fixed in formalin, and subjected to thin-section CT and low-kilovoltage radiography. Informed consent was provided by the patients, and the study was approved by the internal review board at the hospital.

Chest Radiographic Evaluation
Two reviewers independently interpreted the radiographs according to the 1980 International Labor Organization classification of pneumoconiosis [14]. The reviewers were a respiratory physician with a special interest in pneumoconiosis and a thoracic radiologist; both were certified by the National Institute for Occupational Safety and Health. The radiographs were interpreted in random order. Profusion of small opacities was scored with the International Labor Organization grading system on the basis of the viewer's assessment of the concentration of opacities compared with standard radiographs provided by the International Labor Organization [14].

View larger version (135K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A —61-year-old man with inhalational talc pneumoconiosis employed in talc industry for 20 years. Initial chest radiograph shows fine nodular opacities diffusely distributed throughout both lungs.

View larger version (154K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B —61-year-old man with inhalational talc pneumoconiosis employed in talc industry for 20 years. Chest radiograph obtained at 15-year follow-up examination shows fine nodules and large opacity in upper zone of right lung and middle zone of left lung.

View larger version (120K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1C —61-year-old man with inhalational talc pneumoconiosis employed in talc industry for 20 years. Axial supine thin-section CT scan shows well-defined (arrowheads) and ill-defined (arrows) small nodular opacities mainly distributed in centrilobular location.

View larger version (90K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1D —61-year-old man with inhalational talc pneumoconiosis employed in talc industry for 20 years. Axial supine thin-section CT scan obtained at mediastinal settings shows large opacity and lymph nodes containing high-attenuation material.

View larger version (154K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A —57-year-old man with inhalational talc pneumoconiosis employed in talc industry for 14 years. Chest radiograph shows small nodular opacities and large opacity.

View larger version (151K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B —57-year-old man with inhalational talc pneumoconiosis employed in talc industry for 14 years. Chest radiograph obtained at 13-year follow-up examination shows large opacities associated with bilateral superior retraction of hila.

View larger version (117K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2C —57-year-old man with inhalational talc pneumoconiosis employed in talc industry for 14 years. Axial supine thin-section CT scan shows bandlike opacity parallel to pleural surface.

View larger version (91K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2D —57-year-old man with inhalational talc pneumoconiosis employed in talc industry for 14 years. In vitro low-kilovoltage radiograph of inflated and fixed lung. Crescent-shaped large opacity and small nodular opacities are evident.

View larger version (89K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2E —57-year-old man with inhalational talc pneumoconiosis employed in talc industry for 14 years. In vitro thin-section CT scan of inflated and fixed lung. Crescent-shaped large opacity is attached to pleural surface. Subpleural line (arrows) is evident.

View larger version (139K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2F —57-year-old man with inhalational talc pneumoconiosis employed in talc industry for 14 years. Photograph of histologic section through crescentic large opacity shows diffuse fibrosis and proliferation of dust-laden macrophages and multinucleated giant cells (arrows). (H and E, x4)

CT Images
Thin-section CT was performed with a Quantex Plus or a LightSpeed CT unit (GE Healthcare). All CT scans were obtained at maximal inspiration with 1.5-mm collimation at 20-mm intervals. CT scans at maximal expiration were added for two patients whose inspiratory CT scans showed lobular low-attenuation areas. Scanning extended from the lung apices to below the costophrenic angles. Images were reconstructed with a high-spatial-frequency algorithm. CT scans were obtained with the patient in the supine position. The images were photographed on hard copy at lung (window width, 1,200 H; level, -700 H) and soft-tissue (window width, 300 H; level, 10 H) settings.

CT Evaluation
The CT images were reviewed independently by two chest radiologists unaware of the clinical and radiographic data. The final decisions on CT findings were reached by consensus. The reviewers evaluated the scans for the presence and distribution of ground-glass opacity, septal lines, subpleural lines, small rounded opacities, centrilobular nodules, small irregular opacities, large opacities, traction bronchiectasis, honeycombing, lobular low-attenuation areas, and emphysema [15, 16].

View larger version (125K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2G —57-year-old man with inhalational talc pneumoconiosis employed in talc industry for 14 years. Photomicrograph of biopsy specimen examined under polarized light shows fibrosis contains large accumulations of strongly birefringent dust particles.

View larger version (110K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2H —57-year-old man with inhalational talc pneumoconiosis employed in talc industry for 14 years. Histologic section from area of subpleural line shows peribronchiolar fibrosis joined by collapse and fibrosis of alveoli along thickened pleura (arrows). (H and E, x1.6)

For craniocaudal distribution, the upper lung zone was defined as the region above the tracheal carina; the middle zone as the region between the carina and inferior pulmonary veins; and the lower zone as the region below the inferior pulmonary veins. Calcified or noncalcified pleural plaques and lymph node enlargement with the short axis exceeding 1 cm were also recorded.

Results

Top Abstract Introduction Materials and Methods Results Discussion References

 
Chest Radiographic Findings
The main abnormality found on initial chest radiographs was small rounded opacities of the p type (Fig. 1A). All zones usually were affected. In one patient, the opacities had upper lung zone predominance, and in another middle lung zone predominance. Small irregular opacities of the s and t types predominated in the lower lung zones in one patient. The profusion and type of small opacities are presented in Table 1. Large opacities greater than 1 cm in diameter were found in seven patients on initial chest radiographs (Fig. 2A). The large opacities were distributed in the upper lung zones in two patients, in the middle lung zones in one patient, in the upper and middle lung zones in three patients, and in all zones in one patient.

Follow-up examinations of two of the 14 patients showed the small opacities had progressed. Profusion had changed from 2/2 to 2/3. In another patient, profusion of small opacities decreased from 2/2 to 2/1, but that of large opacities increased. The other 11 patients had no change during the follow-up period. The size and number of large opacities had increased by the follow-up examination in all seven patients (Figs. 1B and 2B). At the followup examinations of another two patients, large opacities were present in the upper, middle, and lower zones. Progression of large opacities was found to be a difference of one grade in four patients (from 0 to A in one and from B to C in three) and a difference of two grades in one patient (from 0 to B). In another four patients, progression was within the same grade (from A to A in two, B to B in one, and C to C in one). In these four patients, progression of large opacities was found at side-by-side review of the radiographs in chronologic order. Lymph node enlargement was found in two patients. Pleural plaques were found in no patients.

Thin-Section CT Findings
The thin-section CT findings for the 14 patients are presented in Table 2. The main CT finding in 12 of 14 patients was diffusely distributed centrilobular nodules 1-2 mm in diameter. In one patient, the centrilobular nodules had upper lung predominance; in another patient, middle lung predominance; and in 10 patients, no zonal predominance. A few welldefined discrete nodules were found in these 12 patients, mingled with centrilobular nodules in all zones (Fig. 1C). Well-defined nodules ranged from 2 to 4 mm in diameter and were in a centrilobular or subpleural location. In one patient, CT scans showed small irregular opacities and honeycombing in the lower lung zones and diffusely distributed centrilobular nodules in all zones. In another patient, CT showed large opacities in the upper and middle lung zones and a few well-defined small rounded opacities distributed in all lung zones.

Large opacities greater than 1 cm in diameter were found in nine patients. The large opacities involved all lung zones in four patients, the upper zones in one patient, the upper and middle zones in three patients, and the middle and lower zones in one patient. The large opacities were irregular, round, or crescent-shaped (Fig. 2C). Most large opacities were totally of high attenuation (Fig. 1D).

View larger version (123K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3 —66-year-old man with inhalational talc pneumoconiosis. Axial supine thin-section CT scan shows subpleural line.

View larger version (135K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4 —77-year-old man with inhalational talc pneumoconiosis. Histopathologic photograph shows nodular fibrosis (arrows) adjacent to vessels or bronchi. (H and E, x1.25)

There was good agreement between observers. In two cases there was disagreement about chest radiographs and in one case about CT scans.

Radiologic-Pathologic Correlation
The postmortem low-kilovoltage radiographs and thin-section CT scans of one patient showed a crescent-shaped large opacity, subpleural lines, and small nodules (Figs. 2D and 2E). The crescent-shaped large opacity corresponded histologically to diffuse fibrosis with proliferation of dustladen macrophages and multinucleated giant cells (Fig. 2F). Microscopic evaluation with polarized light revealed dense accumulations of birefringent dust particles in fibrosis (Fig. 2G). The subpleural lines corresponded histologically to peribronchiolar fibrosis joined by collapse and fibrosis of the alveoli along the inner chest wall (Fig. 2H).

In six autopsy cases, the lungs exhibited varying degrees of fibrosis. Nodular fibrosis was adjacent to the vessels or bronchi (Fig. 4). Dense accumulations of birefringent dust particles were found in fibrosis and lymph nodes, but calcification was not found in fibrosis or lymph nodes. Pleural plaques were found at histopathologic examination in three of six autopsy cases. In these three cases, the premortem CT scans showed pleural plaques.

Discussion

Top Abstract Introduction Materials and Methods Results Discussion References

 
Three forms of talc pneumoconiosis by inhalation have been described in the literature: talc asbestosis, talc silicosis, and talcosis. Talc asbestosis is produced by inhalation of talc with asbestiform fibers. The findings of talc silicosis caused by talc mined with highsilica-content mineral are identical to those of silicosis. Talc free of silica and asbestiform minerals may be fibrogenic [3, 4, 8, 17].

In our cases, the predominant radiographic abnormalities were small nodular opacities affecting all lung zones. Small irregular opacities were rare. Although progression of small rounded opacities was rare during long-term follow-up, most large opacities progressed. Slight pleural plaques and lymph node enlargement not found on chest radiographs were identified on thin-section CT scans.

As in patients with silicosis, in our pneumoconiosis patients, small rounded opacities, septal lines, large opacities, and lymph node enlargement were predominant findings on CT. The characteristic radiologic abnormality in silicosis is small, well-circumscribed nodules usually 2-5 mm in diameter and mainly involving the upper and posterior lung zones [12, 18]. In our patients, however, centrilobular nodules were the prominent finding, and the distribution was diffuse. In silicosis, large opacities usually involve the upper lung zones, and various types of calcification of large opacities are found, mostly punctate rather than linear or massive. In our patients, large opacities were distributed in all lung zones, and large opacities were of high density. Unlike the findings in patients with silicosis, pleural plaques were seen in our patients (Table 3). One of our patients had the CT findings of asbestosis: diffuse linear interstitial pattern predominantly distributed in the lower zones of the lungs [12, 19]. Diffusely distributed centrilobular nodules unlike the findings of asbestosis were found on that patient's CT scans.

Subpleural curvilinear lines are defined as linear areas of increased attenuation within 1 cm of the pleura and parallel to the inner chest wall. The pathologic correlate of subpleural lines represents peribronchiolar fibrotic thickening combined with flattening and collapse of the alveoli due to fibrosis in asbestosis [20, 21]. Subpleural curvilinear lines are considered to be caused by other pathologic processes. This finding corresponds to conditions such as platelike atelectasis in the corticomedullary junction of the lung [22], interstitial edema from pulmonary congestion [23], and subpleural lymphatic network after lymphography [24].

The main CT findings in three patients with inhalational pulmonary talcosis described by Marchiori and associates [13] were small centrilobular and subpleural nodules associated with conglomerated masses containing foci of high attenuation. Our findings were similar to those of Marchiori et al. In our study, centrilobular nodules histopathologically corresponded to nodular fibrosis and deposition of talc particles adjacent to the vessels or bronchi. Our study revealed that increased CT densities of lymph nodes and large opacities were caused by large numbers of talc particles.

The radiographic findings of IV administration of talc include large, irregular, nodular densities or consolidations in the upper parts of the middle fields of the lungs that may rapidly progress into large masses or massive consolidations. Widespread irregular nodules also occur [9-11]. The CT findings in patients with pulmonary talcosis resulting from chronic IV drug abuse include widespread ground-glass attenuation, a diffuse fine nodular pattern, and a combination of nodules and lower lobe panacinar emphysema. Confluent perihilar masses with areas of high attenuation are also seen [9-11]. The CT findings in our patients resembled those of pulmonary talcosis due to IV administration. A diffuse fine nodular pattern and large opacities containing high-attenuation material are seen in both IV administration and inhalation. Although lobular low-attenuation areas were seen, lower lobe panacinar emphysema was not seen in our patients. To our knowledge, slight lymph node enlargement with high-attenuation material has not been reported in talcosis by IV administration. Talcosis from IV administration of talc can be differentiated from the inhalation of talc on the basis of histologic findings and size of the talc particles. The mean particle diameter is far greater in IV-administrated talc, usually exceeding 10 µm compared with 4 µm for inhaled talc [25].

We did not analyze the nature of the mineral exposure in our patients, so it is not clear whether our findings were caused by contaminant fibers. The composition of commercially available talc is quite variable from region to region and from industry to industry. Pleural plaques are seen in workers exposed to talc contaminated with asbestos and talc free of asbestos [26]. Our study had limitations. It was retrospective, and the preliminary conclusions were based on findings in a relatively small number of patients.

In summary, serial chest radiography showed that in talc pneumoconiosis, large opacities progressed more often than small rounded opacities. CT scans depicted pleural plaques and lymph node enlargement with high-attenuation material not identified on chest radiography. The distribution of small rounded opacities was diffuse, whereas large opacities were present in all lung zones. Unlike silicosis, in talc pneumoconiosis there was no predilection for upper lung zones. Pleural plaques and subpleural lines and small rounded opacities were evident. CT showed high-attenuation material in large opacities and lymph node enlargement caused by large numbers of talc particles. The CT findings of talc pneumoconiosis are not specific and can occur in asbestosis and silicosis. Although the combination of these findings is seen in patients with mixed dust exposure, talc pneumoconiosis should be considered in patients with diffusely distributed centrilobular nodules, dense large opacities, dense lymph nodes, and pleural plaques.

References

Top Abstract Introduction Materials and Methods Results Discussion References

 

1. Thorel C. Talc lung: a contribution to the pathological anatomy of pneumoconiosis. Beitr Pathol Anat Allgem Pathol1896; 20:85 -101
2. Vallyathan NV, Craighead JE. Pulmonary pathology in workers exposed to nonasbestiform talc. Hum Pathol 1981;12 : 28-35[Medline]
3. Gibbs AE, Pooley FD, Griffiths DM, Mitha R, Craighead JE, Ruttner JR. Talc pneumoconiosis: a pathologic and mineralogic study. Hum Pathol 1992; 23:1344 -1354[CrossRef][Medline]
4. Feigin DS. Talc: understanding its manifestations in the chest. AJR 1986; 146:295 -301[Abstract/Free Full Text]
5. Leophonte P, Didier A. French talc pneumoconiosis. In: Bignon J, ed., Health-related effects of phyllosilicates. Berlin, Germany: Springer Verlag, 1990:203 -209
6. Porro FW, Patton JR, Hobbs AA. Pneumoconiosis in the talc industry. AJR 1942; 47:507 -524
7. Kleinfeld M, Messite J, Tabershaw IR. Talc pneumoconiosis. AMA Arch Ind Health 1955;12 : 66-72[Medline]
8. Feigin DS. Misconceptions regarding the pathogenicity of silicas and silicates. J Thorac Imaging 1989;4 : 68-80[Medline]
9. Padley SP, Adler BD, Staples CA, Miller RR, Müller NL. Pulmonary talcosis: CT findings in three cases. Radiology 1993;186 : 125-127[Abstract/Free Full Text]
10. Ward S, Heyneman LE, Reittner P, Kazerooni EA, Godwin JD, Müller NL. Talcosis associated with IV abuse of oral medications: CT findings. AJR 2000;174 : 789-793[Abstract/Free Full Text]
11. Stern EJ, Frank MS, Schutz JF, Glenny RW, Schmidt RA, Godwin JD. Panlobular pulmonary emphysema caused by IV injection of methylphenidate (Ritalin): findings on chest radiographs and CT scans. AJR 1994; 162:555 -560[Abstract/Free Full Text]
12. Akira M. High-resolution CT in the evaluation of occupational and environmental disease. Radiol Clin North Am2002; 40:43 -59[CrossRef][Medline]
13. Marchiori E, Souza AS Jr, Müller NL. Inhalational pulmonary talcosis: high-resolution CT findings in 3 patients. J Thorac Imaging 2004; 19:41 -44[CrossRef][Medline]
14. Guidelines for the use of ILO international classification of radiographs of pneumoconiosis, rev ed. Occupational Safety and Health Series no. 22. Geneva, Switzerland: International Labor Organization, 1980
15. Austin JH, Müller NL, Friedman PJ, et al. Glossary of terms for CT of the lungs: recommendations of the nomenclature committee of the Fleischner Society. Radiology 1996;200 : 327-331[Free Full Text]
16. Im JG, Kim SH, Chung MJ, Koo JM, Han MC. Lobular low attenuation of the lung parenchyma on CT: evaluation of forty-eight patients. J Comput Assist Tomogr 1996;20 : 756-762[CrossRef][Medline]
17. Lockey JE. Nonasbestos fibrous minerals. Clin Chest Med 1981; 2:203 -218[Medline]
18. Kim KI, Kim CW, Lee MK, et al. Imaging of occupational lung disease. RadioGraphics 2001;21 : 1371-1391[Abstract/Free Full Text]
19. Aberle DR, Gamsu G, Ray CS, Feuerstein IM. Asbestos-related pleural and parenchymal fibrosis: detection with thin-section CT. Radiology 1988;166 : 729-734[Abstract/Free Full Text]
20. Akira M, Yokoyama K, Yamamoto S, et al. Early asbestosis: evaluation with high-resolution CT. Radiology1991; 178:409 -416[Abstract/Free Full Text]
21. Yoshimura H, Hatakeyama M, Otsuji H, et al. Pulmonary asbestosis: CT study of subpleural curvilinear shadow. Radiology1986; 158:653 -658[Abstract/Free Full Text]
22. Kubota H, Hosoya T, Kato M, Uchimura F, Itagaki T, Yamaguchi K. Plate-like atelectasis at the corticomedullary junction of the lung: CT observation and hypothesis. Radiat Med1983; 1:305 -310[Medline]
23. Arai K, Takashima T, Matsui O, Kadoya M, Kamimura R. Transient subpleural curvilinear shadow caused by pulmonary congestion. J Comput Assist Tomogr 1990;14 : 87-88[Medline]
24. Pilate I, Marcelis S, Timmerman H, Beeckman P, Osteaux MJ. Pulmonary asbestosis: CT study of subpleural curvilinear shadow. (letter) Radiology 1987;164 : 584[Medline]
25. Abraham JL, Brambilla C. Particle size for differentiation between inhalation and injection pulmonary talcosis. Environ Res 1980; 21:94 -96[Medline]
26. Wegman DH, Peters JM, Boundy MG, Smith TJ. Evaluation of respiratory effects in miners and millers exposed to talc free of asbestos and silica. Br J Ind Med 1982;39 : 233-238[Medline]

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				L. K. Strack and S. K. Aberegg A 53-Year-Old Woman With Chronic Pain and Progressive Dyspnea and Cough Chest, May 1, 2009; 135(5): 1380 - 1383. [Full Text] [PDF]

This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Akira, M. Articles by Morinaga, K. Search for Related Content PubMed PubMed Citation Articles by Akira, M. Articles by Morinaga, K. Social Bookmarking                      What's this? Hotlight (NEW!) What's Hotlight?