Cryptococcosis other diagnostic studies: Difference between revisions
No edit summary |
No edit summary |
||
Line 3: | Line 3: | ||
{{CMG}} | {{CMG}} | ||
==Overview== | ==Overview== | ||
Other diagnostic studies helpful for diagnosis of cryptococcal infection include demonstration of the budding yeast on India ink stain, staining the polysaccharide cell wall using Mucicarmine stain, detection of cryptococcal antigen in CSF and a positive culture for | Other diagnostic studies helpful for diagnosis of cryptococcal infection include demonstration of the budding yeast on India ink stain, staining the polysaccharide cell wall using Mucicarmine stain, detection of cryptococcal antigen in [[CSF]] and a positive culture for [[Cryptococcus neoformans]]. | ||
==Other Diagnostic studies== | ==Other Diagnostic studies== | ||
Line 9: | Line 9: | ||
*[[Mucicarmine]] stain provides specific staining of the [[polysaccharide]] cell wall. | *[[Mucicarmine]] stain provides specific staining of the [[polysaccharide]] cell wall. | ||
*[[Antigen]] detection in [[CSF]] is useful for the diagnosis of cryptococcal meningitis. | *[[Antigen]] detection in [[CSF]] is useful for the diagnosis of cryptococcal meningitis. | ||
*Cryptococcus neoformans can be cultured from sputum or bronchoalveolar lavage or transbronchial lung biopsy specimen or pleural fluid or pleural biopsy specimen in patients with pulmonary cryptococcosis.<ref name="pmid2225944">{{cite journal| author=Chechani V, Kamholz SL| title=Pulmonary manifestations of disseminated cryptococcosis in patients with AIDS. | journal=Chest | year= 1990 | volume= 98 | issue= 5 | pages= 1060-6 | pmid=2225944 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2225944 }} </ref> | *[[Cryptococcus neoformans]] can be cultured from [[sputum]] or [[bronchoalveolar lavage]] or transbronchial lung [[biopsy]] specimen or [[pleural fluid]] or pleural [[biopsy]] specimen in patients with pulmonary [[cryptococcosis]].<ref name="pmid2225944">{{cite journal| author=Chechani V, Kamholz SL| title=Pulmonary manifestations of disseminated cryptococcosis in patients with AIDS. | journal=Chest | year= 1990 | volume= 98 | issue= 5 | pages= 1060-6 | pmid=2225944 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2225944 }} </ref> | ||
====Culture==== | ====Culture==== | ||
*The gold standard for diagnosing cryptococcal infection | *The gold standard for diagnosing cryptococcal infection.<ref name="cdc">Information for Healthcare Professionals about C. neoformans Infection. Centers for Disease Control and Prevention (2015). http://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/health-professionals.html Accessed on December 31, 2015</ref> | ||
*Blood cultures may be positive in | *[[Blood cultures]] may be positive in severe infections. | ||
====Microscopy==== | ====Microscopy==== | ||
*India Ink can be performed on CSF to quickly visualize Cryptococcus cells under a microscope; however, it can have limited sensitivity. <ref name=cdc>Information for Healthcare Professionals about C. neoformans Infection. Centers for Disease Control and Prevention (2015). http://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/health-professionals.html Accessed on December 31, 2015</ref> | *India Ink can be performed on [[CSF]] to quickly visualize [[Cryptococcus neoformans|Cryptococcus]] cells under a microscope; however, it can have limited sensitivity. <ref name="cdc">Information for Healthcare Professionals about C. neoformans Infection. Centers for Disease Control and Prevention (2015). http://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/health-professionals.html Accessed on December 31, 2015</ref> | ||
*Many laboratories in the United States no longer perform this test. <ref name=aids>Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed on December 31, 2015.</ref> | *Many laboratories in the United States no longer perform this test. <ref name="aids">Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed on December 31, 2015.</ref> | ||
*Histopathology for detection of narrow-based budding yeasts in tissue can also be used.<ref name=cdc>Information for Healthcare Professionals about C. neoformans Infection. Centers for Disease Control and Prevention (2015). http://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/health-professionals.html Accessed on December 31, 2015</ref> | *[[Histopathology]] for detection of narrow-based budding yeasts in tissue can also be used.<ref name="cdc">Information for Healthcare Professionals about C. neoformans Infection. Centers for Disease Control and Prevention (2015). http://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/health-professionals.html Accessed on December 31, 2015</ref> | ||
====Antigen detection==== | ====Antigen detection==== | ||
* Antigen detection can be used on CSF or serum for detection of early, asymptomatic cryptococcal infection in HIV-infected patients. | * [[Antigen detection test|Antigen detection]] can be used on [[CSF]] or serum for detection of early, asymptomatic cryptococcal infection in [[HIV]]-infected patients. | ||
* It has a higher sensitivity than microscopy or culture.<ref name=cdc>Information for Healthcare Professionals about C. neoformans Infection. Centers for Disease Control and Prevention (2015). http://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/health-professionals.html Accessed on December 31, 2015</ref> | * It has a higher [[sensitivity]] than [[microscopy]] or culture.<ref name="cdc">Information for Healthcare Professionals about C. neoformans Infection. Centers for Disease Control and Prevention (2015). http://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/health-professionals.html Accessed on December 31, 2015</ref> | ||
* CSF CrAg is usually positive in patients with cryptococcal meningoencephalitis. Serum CrAg is usually positive in both meningeal and non-meningeal infection and may be present weeks to months before symptom onset.<ref name=aids>Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed on December 31, 2015.</ref> | * [[CSF]] CrAg is usually positive in patients with [[Cryptococcosis|cryptococcal]] [[meningoencephalitis]]. [[Serum]] CrAg is usually positive in both [[meningeal]] and non-meningeal infection and may be present weeks to months before symptom onset.<ref name="aids">Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed on December 31, 2015.</ref> | ||
* A positive serum CrAg should prompt a lumbar puncture to rule out meningeal disease.<ref name=aids>Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed on December 31, 2015.</ref> | * A positive serum CrAg should prompt a [[lumbar puncture]] to rule out meningeal disease.<ref name="aids">Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed on December 31, 2015.</ref> | ||
*Techniques used include:<ref name=cdc>Information for Healthcare Professionals about C. neoformans Infection. Centers for Disease Control and Prevention (2015). http://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/health-professionals.html Accessed on December 31, 2015</ref> | *Techniques used include:<ref name="cdc">Information for Healthcare Professionals about C. neoformans Infection. Centers for Disease Control and Prevention (2015). http://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/health-professionals.html Accessed on December 31, 2015</ref> | ||
:*Latex agglutination (LA) | :*[[Latex agglutination test|Latex agglutination]] (LA) | ||
:*Enzyme immunoassay (EIA) | :*[[Enzyme immunoassay]] (EIA) | ||
:*Lateral flow assay (LFA) | :*Lateral flow assay (LFA) | ||
===CSF Analysis=== | ===CSF Analysis=== | ||
Cryptococcal meningitis may be differentiated from other causes of [[meningitis]] by [[cerebrospinal fluid]] examination as shown below:<ref name="pmid23717798">{{cite journal| author=Le Rhun E, Taillibert S, Chamberlain MC| title=Carcinomatous meningitis: Leptomeningeal metastases in solid tumors. | journal=Surg Neurol Int | year= 2013 | volume= 4 | issue= Suppl 4 | pages= S265-88 | pmid=23717798 | doi=10.4103/2152-7806.111304 | pmc=3656567 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23717798 }} </ref><ref name="pmid24326618">{{cite journal| author=Chow E, Troy SB| title=The differential diagnosis of hypoglycorrhachia in adult patients. | journal=Am J Med Sci | year= 2014 | volume= 348 | issue= 3 | pages= 186-90 | pmid=24326618 | doi=10.1097/MAJ.0000000000000217 | pmc=4065645 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24326618 }} </ref><ref name="pmid22880096">{{cite journal| author=Leen WG, Willemsen MA, Wevers RA, Verbeek MM| title=Cerebrospinal fluid glucose and lactate: age-specific reference values and implications for clinical practice. | journal=PLoS One | year= 2012 | volume= 7 | issue= 8 | pages= e42745 | pmid=22880096 | doi=10.1371/journal.pone.0042745 | pmc=3412827 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22880096 }} </ref><ref name="pmid10654948">{{cite journal| author=Negrini B, Kelleher KJ, Wald ER| title=Cerebrospinal fluid findings in aseptic versus bacterial meningitis. | journal=Pediatrics | year= 2000 | volume= 105 | issue= 2 | pages= 316-9 | pmid=10654948 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10654948 }} </ref><ref name="pmid20610819">{{cite journal| author=Brouwer MC, Tunkel AR, van de Beek D| title=Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. | journal=Clin Microbiol Rev | year= 2010 | volume= 23 | issue= 3 | pages= 467-92 | pmid=20610819 | doi=10.1128/CMR.00070-09 | pmc=2901656 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20610819 }} </ref> | Cryptococcal meningitis may be differentiated from other causes of [[meningitis]] by [[cerebrospinal fluid]] examination as shown below:<ref name="pmid23717798">{{cite journal| author=Le Rhun E, Taillibert S, Chamberlain MC| title=Carcinomatous meningitis: Leptomeningeal metastases in solid tumors. | journal=Surg Neurol Int | year= 2013 | volume= 4 | issue= Suppl 4 | pages= S265-88 | pmid=23717798 | doi=10.4103/2152-7806.111304 | pmc=3656567 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23717798 }} </ref><ref name="pmid24326618">{{cite journal| author=Chow E, Troy SB| title=The differential diagnosis of hypoglycorrhachia in adult patients. | journal=Am J Med Sci | year= 2014 | volume= 348 | issue= 3 | pages= 186-90 | pmid=24326618 | doi=10.1097/MAJ.0000000000000217 | pmc=4065645 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24326618 }} </ref><ref name="pmid22880096">{{cite journal| author=Leen WG, Willemsen MA, Wevers RA, Verbeek MM| title=Cerebrospinal fluid glucose and lactate: age-specific reference values and implications for clinical practice. | journal=PLoS One | year= 2012 | volume= 7 | issue= 8 | pages= e42745 | pmid=22880096 | doi=10.1371/journal.pone.0042745 | pmc=3412827 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22880096 }} </ref><ref name="pmid10654948">{{cite journal| author=Negrini B, Kelleher KJ, Wald ER| title=Cerebrospinal fluid findings in aseptic versus bacterial meningitis. | journal=Pediatrics | year= 2000 | volume= 105 | issue= 2 | pages= 316-9 | pmid=10654948 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10654948 }} </ref><ref name="pmid20610819">{{cite journal| author=Brouwer MC, Tunkel AR, van de Beek D| title=Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. | journal=Clin Microbiol Rev | year= 2010 | volume= 23 | issue= 3 | pages= 467-92 | pmid=20610819 | doi=10.1128/CMR.00070-09 | pmc=2901656 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20610819 }} </ref> | ||
{| style="border: 0px; font-size: 90%; margin: 3px;" align=center | {| style="border: 0px; font-size: 90%; margin: 3px;" align="center" | ||
|+ | |+ | ||
! style="background: #4479BA; width: 150px;" | {{fontcolor|#FFF|Cerebrospinal fluid level}} | ! style="background: #4479BA; width: 150px;" | {{fontcolor|#FFF|Cerebrospinal fluid level}} |
Revision as of 17:07, 12 June 2017
Cryptococcosis Microchapters |
Diagnosis |
---|
Treatment |
Case Studies |
Cryptococcosis other diagnostic studies On the Web |
American Roentgen Ray Society Images of Cryptococcosis other diagnostic studies |
Risk calculators and risk factors for Cryptococcosis other diagnostic studies |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Other diagnostic studies helpful for diagnosis of cryptococcal infection include demonstration of the budding yeast on India ink stain, staining the polysaccharide cell wall using Mucicarmine stain, detection of cryptococcal antigen in CSF and a positive culture for Cryptococcus neoformans.
Other Diagnostic studies
- India ink or fungal wet mount of CSF will demonstrate a (budding yeast).
- Mucicarmine stain provides specific staining of the polysaccharide cell wall.
- Antigen detection in CSF is useful for the diagnosis of cryptococcal meningitis.
- Cryptococcus neoformans can be cultured from sputum or bronchoalveolar lavage or transbronchial lung biopsy specimen or pleural fluid or pleural biopsy specimen in patients with pulmonary cryptococcosis.[1]
Culture
- The gold standard for diagnosing cryptococcal infection.[2]
- Blood cultures may be positive in severe infections.
Microscopy
- India Ink can be performed on CSF to quickly visualize Cryptococcus cells under a microscope; however, it can have limited sensitivity. [2]
- Many laboratories in the United States no longer perform this test. [3]
- Histopathology for detection of narrow-based budding yeasts in tissue can also be used.[2]
Antigen detection
- Antigen detection can be used on CSF or serum for detection of early, asymptomatic cryptococcal infection in HIV-infected patients.
- It has a higher sensitivity than microscopy or culture.[2]
- CSF CrAg is usually positive in patients with cryptococcal meningoencephalitis. Serum CrAg is usually positive in both meningeal and non-meningeal infection and may be present weeks to months before symptom onset.[3]
- A positive serum CrAg should prompt a lumbar puncture to rule out meningeal disease.[3]
- Techniques used include:[2]
- Latex agglutination (LA)
- Enzyme immunoassay (EIA)
- Lateral flow assay (LFA)
CSF Analysis
Cryptococcal meningitis may be differentiated from other causes of meningitis by cerebrospinal fluid examination as shown below:[4][5][6][7][8]
Cerebrospinal fluid level | Normal level | Bacterial meningitis[7] | Viral meningitis[7] | Cryptococcal meningitis | Tuberculous meningitis[9] | Malignant meningitis[4] |
---|---|---|---|---|---|---|
Cells/ul | < 5 | >300 | 10-1000 | 10-500 | 50-500 | >4 |
Cells | Lymphocyte:Monocyte 7:3 | Granulocyte > Lymphocyte | Lymphocyte > Granulocyte | Lympho.>Granulocyte | Lymphocytes | Lymphocytes |
Total protein (mg/dl) | 45-60 | Typically 100-500 | Normal or slightly high | High | Typically 100-200 | >50 |
Glucose ratio (CSF/plasma)[5] | > 0.5 | < 0.3 | > 0.6 | <0.3 | < 0.5 | <0.5 |
Lactate (mmols/l)[6] | < 2.1 | > 2.1 | < 2.1 | >3.2 | > 2.1 | >2.1 |
Others | ICP:6-12 (cm H2O) | CSF gram stain, CSF culture, CSF bacterial antigen | PCR of HSV-DNA, VZV | CSF gram stain, CSF india ink | PCR of TBC-DNA | CSF tumor markers such as alpha fetoproteins, CEA |
Gallery
-
Cryptococcosis of lung in patient with AIDS. From Public Health Image Library (PHIL). [10]
-
Cryptococcosis of lung in patient with AIDS. Mucicarmine stain. From Public Health Image Library (PHIL). [10]
-
Cryptococcosis of lung in patient with AIDS. Methenamine silver stain. From Public Health Image Library (PHIL). [10]
-
Micrograph depicts the histopathologic changes associated with cryptococcosis of the spleen. From Public Health Image Library (PHIL). [10]
-
Micrograph depicts the histopathologic changes associated with cryptococcosis of an adrenal gland. From Public Health Image Library (PHIL). [10]
-
Micrograph depicts the histopathologic changes associated with cryptococcosis of an adrenal gland. From Public Health Image Library (PHIL). [10]
-
Micrograph depicts the histopathologic changes associated with cryptococcosis of the lung using GMS stain. From Public Health Image Library (PHIL). [10]
-
Micrograph depicts the histopathologic changes associated with cryptococcosis of the lung using Mucicarmine stain. From Public Health Image Library (PHIL). [10]
-
Micrograph depicts histopathologic changes due to cryptococcosis of the liver. From Public Health Image Library (PHIL). [10]
-
Cryptococcus neoformans fungi from a liver specimen, and stained using the periodic acid-Schiff staining technique (980X mag). From Public Health Image Library (PHIL). [10]
-
Methenamine silver-stained photomicrograph of a lung lesion tissue specimen, reveals some morphology associated with the disease cryptococcosis (800X mag). From Public Health Image Library (PHIL). [10]
-
Photomicrograph of a lung lesion tissue specimen, reveals some morphology associated with the disease cryptococcosis (800x mag). From Public Health Image Library (PHIL). [10]
-
Periodic acid-Schiff-stained photomicrograph revealed some of the histopathologic details associated with a disseminated Cryptococcus sp. infection involving the liver (980x mag). From Public Health Image Library (PHIL). [10]
References
- ↑ Chechani V, Kamholz SL (1990). "Pulmonary manifestations of disseminated cryptococcosis in patients with AIDS". Chest. 98 (5): 1060–6. PMID 2225944.
- ↑ 2.0 2.1 2.2 2.3 2.4 Information for Healthcare Professionals about C. neoformans Infection. Centers for Disease Control and Prevention (2015). http://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/health-professionals.html Accessed on December 31, 2015
- ↑ 3.0 3.1 3.2 Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed on December 31, 2015.
- ↑ 4.0 4.1 Le Rhun E, Taillibert S, Chamberlain MC (2013). "Carcinomatous meningitis: Leptomeningeal metastases in solid tumors". Surg Neurol Int. 4 (Suppl 4): S265–88. doi:10.4103/2152-7806.111304. PMC 3656567. PMID 23717798.
- ↑ 5.0 5.1 Chow E, Troy SB (2014). "The differential diagnosis of hypoglycorrhachia in adult patients". Am J Med Sci. 348 (3): 186–90. doi:10.1097/MAJ.0000000000000217. PMC 4065645. PMID 24326618.
- ↑ 6.0 6.1 Leen WG, Willemsen MA, Wevers RA, Verbeek MM (2012). "Cerebrospinal fluid glucose and lactate: age-specific reference values and implications for clinical practice". PLoS One. 7 (8): e42745. doi:10.1371/journal.pone.0042745. PMC 3412827. PMID 22880096.
- ↑ 7.0 7.1 7.2 Negrini B, Kelleher KJ, Wald ER (2000). "Cerebrospinal fluid findings in aseptic versus bacterial meningitis". Pediatrics. 105 (2): 316–9. PMID 10654948.
- ↑ Brouwer MC, Tunkel AR, van de Beek D (2010). "Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis". Clin Microbiol Rev. 23 (3): 467–92. doi:10.1128/CMR.00070-09. PMC 2901656. PMID 20610819.
- ↑ Caudie C, Tholance Y, Quadrio I, Peysson S (2010). "[Contribution of CSF analysis to diagnosis and follow-up of tuberculous meningitis]". Ann Biol Clin (Paris). 68 (1): 107–11. doi:10.1684/abc.2010.0407. PMID 20146981.
- ↑ 10.00 10.01 10.02 10.03 10.04 10.05 10.06 10.07 10.08 10.09 10.10 10.11 10.12 "Public Health Image Library (PHIL)".