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{{Pleural effusion}}
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==Overview==
==Overview==
The most common causes of transudative pleural effusions in the United States are [[heart failure|left ventricular failure]], [[pulmonary embolism]], and [[cirrhosis]] (causing hepatic hydrothorax), while the most common causes of exudative pleural effusions are bacterial [[pneumonia]], cancer (with [[lung cancer]], [[breast cancer]], and [[lymphoma]] causing approximately 75% of all malignant pleural effusions), viral infection, and [[pulmonary embolism]].  Although pulmonary embolism can produce either transudative or exudative pleural effusions, the latter is more common.
Common causes of transudative pleural effusion include [[heart failure|left ventricular failure]], [[nephrotic syndrome]], and [[cirrhosis]].<ref name="pmid27164734">{{cite journal| author=Chawla RK, Madan A, Chawla A, Arora HN, Chawla K| title=Bilateral Pleural Effusion: A Rare Case Report. | journal=Indian J Chest Dis Allied Sci | year= 2015 | volume= 57 | issue= 4 | pages= 243-5 | pmid=27164734 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27164734  }} </ref><ref name="pmid26963358">{{cite journal| author=Gilbert CR, Yarmus LB, Feller-Kopman DJ, Lee HJ, Gorden JA| title=The Undefined Value of Pleural Interventions in Advanced Heart Failure and Recurrent Pleural Effusions. | journal=Ann Am Thorac Soc | year= 2016 | volume= 13 | issue= 3 | pages= 447-8 | pmid=26963358 | doi=10.1513/AnnalsATS.201512-825LE | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26963358  }} </ref><ref name="pmid23494296">{{cite journal| author=Riccio E, Argentino G, Pisani A, Memoli B| title=Pleural effusion in peritoneal dialysis: overload or leakage? | journal=Clin Exp Nephrol | year= 2013 | volume= 17 | issue= 6 | pages= 907 | pmid=23494296 | doi=10.1007/s10157-013-0794-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23494296  }} </ref><ref name="pmid26305084">{{cite journal| author=Shah S, Robson N, Sajid S| title=Pleuro-Peritoneal Fistula – An Important Condition to Consider in Patients using Peritoneal Dialysis. | journal=Acute Med | year= 2015 | volume= 14 | issue= 2 | pages= 69-71 | pmid=26305084 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26305084  }} </ref><ref name="pmid23853026">{{cite journal| author=Asim M, Hamid EM| title=Pleuroperitoneal leak in a peritoneal dialysis patient. | journal=BMJ Case Rep | year= 2013 | volume= 2013 | issue= | pages=  | pmid=23853026 | doi=10.1136/bcr-2013-200130 | pmc=3736585 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23853026  }} </ref> Common causes of exudative pleural effusions include: bacterial [[pneumonia]], cancer (with [[lung cancer]], [[breast cancer]], and [[lymphoma]] causing approximately 75% of all malignant pleural effusions), viral infection, and [[pulmonary embolism]].<ref name="pmid26897270">{{cite journal| author=Lee J, Lim JK, Lee SY, Yoo SS, Lee SY, Cha SI et al.| title=Neutrophilic Loculated Tuberculous Pleural Effusion: Incidence, Characteristics and Differentiation From Complicated Parapneumonic Effusion. | journal=Am J Med Sci | year= 2016 | volume= 351 | issue= 2 | pages= 153-9 | pmid=26897270 | doi=10.1016/j.amjms.2015.11.010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26897270 }} </ref> Pulmonary embolism may lead to formation of either transudate or exudate, however, an exudate is commonly observed.


==Causes==
==Causes of Transudates==
===Common Causes===
===Most Common Causes===
The most common causes of transudative pleural effusions in the United States are:
Most common causes of transudative pleural effusion include:<ref name="pmid27164734">{{cite journal| author=Chawla RK, Madan A, Chawla A, Arora HN, Chawla K| title=Bilateral Pleural Effusion: A Rare Case Report. | journal=Indian J Chest Dis Allied Sci | year= 2015 | volume= 57 | issue= 4 | pages= 243-5 | pmid=27164734 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27164734  }} </ref><ref name="pmid26963358">{{cite journal| author=Gilbert CR, Yarmus LB, Feller-Kopman DJ, Lee HJ, Gorden JA| title=The Undefined Value of Pleural Interventions in Advanced Heart Failure and Recurrent Pleural Effusions. | journal=Ann Am Thorac Soc | year= 2016 | volume= 13 | issue= 3 | pages= 447-8 | pmid=26963358 | doi=10.1513/AnnalsATS.201512-825LE | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26963358  }} </ref><ref name="pmid23494296">{{cite journal| author=Riccio E, Argentino G, Pisani A, Memoli B| title=Pleural effusion in peritoneal dialysis: overload or leakage? | journal=Clin Exp Nephrol | year= 2013 | volume= 17 | issue= 6 | pages= 907 | pmid=23494296 | doi=10.1007/s10157-013-0794-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23494296  }} </ref><ref name="pmid26305084">{{cite journal| author=Shah S, Robson N, Sajid S| title=Pleuro-Peritoneal Fistula – An Important Condition to Consider in Patients using Peritoneal Dialysis. | journal=Acute Med | year= 2015 | volume= 14 | issue= 2 | pages= 69-71 | pmid=26305084 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26305084  }} </ref><ref name="pmid23853026">{{cite journal| author=Asim M, Hamid EM| title=Pleuroperitoneal leak in a peritoneal dialysis patient. | journal=BMJ Case Rep | year= 2013 | volume= 2013 | issue=  | pages=  | pmid=23853026 | doi=10.1136/bcr-2013-200130 | pmc=3736585 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23853026  }} </ref><ref name="pmid9874325">{{cite journal| author=Butani L, Polinsky MS, Kaiser BA, Baluarte HJ| title=Pleural effusion complicating acute peritoneal dialysis in hemolytic uremic syndrome. | journal=Pediatr Nephrol | year= 1998 | volume= 12 | issue= 9 | pages= 772-4 | pmid=9874325 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9874325  }} </ref><ref name="pmid9035166">{{cite journal| author=Hanna J, Truemper E, Burton E| title=Superior vena cava thrombosis and chylothorax: relationship in pediatric nephrotic syndrome. | journal=Pediatr Nephrol | year= 1997 | volume= 11 | issue= 1 | pages= 20-2 | pmid=9035166 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9035166  }} </ref><ref name="pmid4479274">{{cite journal| author=Jenkins PG, Shelp WD| title=Recurrent pleural transudate in the nephrotic syndrome. A new approach to treatment. | journal=JAMA | year= 1974 | volume= 230 | issue= 4 | pages= 587-8 | pmid=4479274 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4479274  }} </ref>
* [[heart failure|Left ventricular failure]]
* [[heart failure|Left ventricular failure]]
* [[Pulmonary embolism]]
*[[Peritoneal dialysis]]
* [[Cirrhosis]] (causing hepatic hydrothorax)
*[[Hypoalbuminaemia]] ([[nephrotic syndrome]] and [[cirrhosis]] )
The  most common causes of exudative pleural effusions are:
 
===Less Common Causes===
*[[Hypothyroidism]]
*[[Mitral stenosis]]
*[[Pulmonary embolism]] (tends to produce a comparatively small effusion but disproportionate [[dyspnea]] and [[pleuritic pain]]; 80% are exudates, 20% are transudates).
 
===Rare Causes===
*[[Superior vena cava]] obstruction (usually due to lung cancer)
*[[Constrictive pericarditis]]
*[[Ovarian hyperstimulation syndrome|Ovarian hyperstimulation]]
*[[Meigs' syndrome]] (benign [[ovarian tumor]], [[ascites]], and pleural effusion)
 
 
==Causes of Exudates==
===Most Common Causes===
Most common causes of exudative pleural effusion include:<ref name="pmid26897270">{{cite journal| author=Lee J, Lim JK, Lee SY, Yoo SS, Lee SY, Cha SI et al.| title=Neutrophilic Loculated Tuberculous Pleural Effusion: Incidence, Characteristics and Differentiation From Complicated Parapneumonic Effusion. | journal=Am J Med Sci | year= 2016 | volume= 351 | issue= 2 | pages= 153-9 | pmid=26897270 | doi=10.1016/j.amjms.2015.11.010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26897270  }} </ref>
* Bacterial [[pneumonia]]
* Bacterial [[pneumonia]]
* Malignancy ([[Lung cancer]], [[breast cancer]], and [[lymphoma]])
* Malignancy ([[lung cancer]], [[breast cancer]], and [[lymphoma]])
* Viral infection
* [[Pulmonary embolism]]
* [[Pulmonary embolism]]
Other causes of pleural effusion include, [[tuberculosis]] (though pleural fluid smears are rarely positive for AFB, this is the most common cause of pleural effusion in some developing countries), autoimmune disease such as [[systemic lupus erythematosus]], bleeding (often due to chest trauma), chylothorax (most commonly caused by trauma), and accidental infusion of fluids.  Less common causes include, esophageal rupture or pancreatic disease,  intraabdominal abscess, [[rheumatoid arthritis]], asbestos pleural effusion, [[Meig's syndrome]] (ascites and pleural effusion due to a benign ovarian tumor), and [[ovarian hyperstimulation syndrome]].


Pleural effusions may also occur through medical/surgical interventions, including the use of medications (pleural fluid is usually [[eosinophilic]]), [[coronary artery bypass surgery]], abdominal surgery, endoscopic variceal sclerotherapy, [[radiation therapy]], liver or lung transplantation, and intra-or extravascular insertion of central lines.
===Less Common Causes===
*[[Pulmonary infarction]] (usually resulting from pulmonary embolism)
*[[Autoimmune disease]], especially [[rheumatoid arthritis]] and [[systemic lupus erythematosus]]
*[[Asbestos]] exposure
*[[Pancreatitis]]
*Complication of [[acute myocardial infarction]] ([[Dressler's syndrome]])
*[[Tuberculosis]] (TB) (the most common cause of pleural effusion in some developing countries where [[TB]] is endemic)
*[[Multiple myeloma]]<ref name="pmid26875957">{{cite journal| author=Wang Z, Xia G, Lan L, Liu F, Wang Y, Liu B et al.| title=Pleural Effusion in Multiple Myeloma. | journal=Intern Med | year= 2016 | volume= 55 | issue= 4 | pages= 339-45 | pmid=26875957 | doi=10.2169/internalmedicine.55.4733 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26875957  }} </ref>
 
===Rare Causes===


=====Commonly asymptomatic patients presenting with a pleural effusion=====
*[[Yellow nail syndrome]] (yellow nails, [[lymphoedema]], [[pleural effusion]] and [[bronchiectasis]])
*Adverse drug reactions (the most common are [[methotrexate]], [[amiodarone]], [[nitrofurantoin]], and [[phenytoin]])
*Fungal infections
*Accidental infusion of fluids 
*[[Esophageal rupture]] or pancreatic disease
*Intraabdominal abscess
*[[Radiation therapy]]
*Operative procedures as seen in [[coronary artery bypass surgery]], liver or lung transplantation, abdominal surgery, endoscopic variceal sclerotherapy, and insertion of central lines
 
===Common Asymptomatic Patients Presenting with Pleural Effusion===
* [[Asbestosis|Benign asbestos pleural effusion]] (BAPE)
* [[Asbestosis|Benign asbestos pleural effusion]] (BAPE)
* [[Hypoalbuminemia]]
* [[Hypoalbuminemia]]
Line 31: Line 62:
* [[Yellow nail syndrome]]
* [[Yellow nail syndrome]]


=====Typically symptomatic patients presenting with a pleural effusion=====
===Typical Symptomatic Patients Presenting with a Pleural Effusion===
* [[Pneumonia|Bacterial pneumonia]]
* [[Pneumonia|Bacterial pneumonia]]
* [[Pleural effusion]] associated with [[malignancy]]
* [[Pleural effusion]] associated with [[malignancy]]
Line 39: Line 70:
* Postcardiac injury syndrome (PCIS)
* Postcardiac injury syndrome (PCIS)
* [[Pulmonary embolism]]
* [[Pulmonary embolism]]
* [[Tuberculous pleural effusion]]
* Tuberculous pleural effusion
* Viral [[pleurisy]]<ref name="isbn0-7817-6957-4">{{cite book | author = Light, Richard J. | authorlink = | editor = |others = | title = Pleural diseases | edition = | language = | publisher = Lippincott Williams & Wilkins | location = Hagerstwon, MD | year = 2007 |origyear = | pages = |quote = | isbn = 0-7817-6957-4 | oclc = |doi = |url = | accessdate = }}</ref>
* Viral [[pleurisy]]<ref name="isbn0-7817-6957-4">{{cite book | author = Light, Richard J. | authorlink = | editor = |others = | title = Pleural diseases | edition = | language = | publisher = Lippincott Williams & Wilkins | location = Hagerstwon, MD | year = 2007 |origyear = | pages = |quote = | isbn = 0-7817-6957-4 | oclc = |doi = |url = | accessdate = }}</ref>


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==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
{{WH}}
{{WS}}


[[Category:Pulmonology]]
[[Category:Pulmonology]]
[[Category:Emergency medicine]]
[[Category:Emergency medicine]]
 
[[Category:Emergency mdicine]]
{{WH}}
[[Category:Disease]]
{{WS}}
[[Category:Up-To-Date]]
[[Category:Infectious disease]]
[[Category:Cardiology]]
[[Category:Surgery]]

Latest revision as of 23:44, 29 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Prince Tano Djan, BSc, MBChB [2]; Nate Michalak, B.A.

Overview

Common causes of transudative pleural effusion include left ventricular failure, nephrotic syndrome, and cirrhosis.[1][2][3][4][5] Common causes of exudative pleural effusions include: bacterial pneumonia, cancer (with lung cancer, breast cancer, and lymphoma causing approximately 75% of all malignant pleural effusions), viral infection, and pulmonary embolism.[6] Pulmonary embolism may lead to formation of either transudate or exudate, however, an exudate is commonly observed.

Causes of Transudates

Most Common Causes

Most common causes of transudative pleural effusion include:[1][2][3][4][5][7][8][9]

Less Common Causes

Rare Causes


Causes of Exudates

Most Common Causes

Most common causes of exudative pleural effusion include:[6]

Less Common Causes

Rare Causes

Common Asymptomatic Patients Presenting with Pleural Effusion

Typical Symptomatic Patients Presenting with a Pleural Effusion

Causes by Organ System

Cardiovascular Central venous stenosis, congestive heart failure, constrictive pericarditis, Dressler's syndrome, pulmonary embolus, pulmonary hypertension, pulmonary infarction, restrictive cardiomyopathy, superior vena cava syndrome, Uhl anomaly, Wegener's granulomatosis, Churg-Strauss syndrome
Chemical / poisoning No underlying causes
Dermatologic Jaffe-Campanacci syndrome, yellow nail syndrome
Drug Side Effect Bromocriptine, Bosutinib, cabergoline, dasatinib, everolimus, ethanolamine oleate, Hydroxocobalamin, lisuride, Meropenem, Oprelvekin, pergolide, Pertuzumab, piribedil, pramipexole, ropinirole, Sargramostim, minoxidil, sirolimus
Ear Nose Throat No underlying causes
Endocrine Myxedema
Environmental No underlying causes
Gastroenterologic Cirrhosis of liver, esophageal perforation, hepatic failure, pancreatitis, protein losing enteropathy, Whipple's disease, abdominal abscess
Genetic No underlying causes
Hematologic Diffuse large B-cell lymphoma, EBV associated lymphoproliferative syndrome, lymphoma, non-Hodgkin lymphoma, lymphangiomyomatosis
Iatrogenic Abdominal surgery, CABG, central venous catheter, endoscopic variceal sclerotherapy, liver transplantation, lung transplantation, post open heart surgery, radiotherapy
Infectious Disease Abdominal abscess, actinomycosis, anthrax, asbestosis, aspergillosis, atypical mycobacteria, blastomycosis, coccidioidomycosis, empyema, Francisella tularensis , hydatid disease, paragonimiasis, pneumonia, scrub typhus, subphrenic abscess, tuberculosis, Whipple's disease
Musculoskeletal / Ortho Diaphragmatic hernia, Gorham's disease, Rheumatoid arthritis
Neurologic Jaffe-Campanacci syndrome, Neurofibromatosis
Nutritional / Metabolic Malnutrition
Obstetric/Gynecologic Fetal indomethacin syndrome,[12] ovarian hyperstimulation syndrome
Oncologic Adenocarcinoma of lung, breast cancer, diffuse large B-cell lymphoma, EBV associated lymphoproliferative syndrome, Kaposi sarcoma, lung cancer, lymphoma, malignancy, Meigs' syndrome, mesothelioma, non-Hodgkin lymphoma, neurofibromatosis, bronchial neoplasm, bronchogenic carcinoma, lung cancer
Opthalmologic No underlying causes
Overdose / Toxicity No underlying causes
Psychiatric No underlying causes
Pulmonary bronchial neoplasm, bronchogenic carcinoma, chylothorax, extensive atelectasis, extramedullary haemopoiesis, haemothorax, lung cancer, lupus pleuritis, lymphangiomyomatosis, pleurisy, pleuritis, pulmonary edema, recurrent polyserositis, urinothorax, yellow nail syndrome , empyema, pneumonia, tuberculosis, Adenocarcinoma of lung, Lung cancer, Meigs' syndrome, Mesothelioma, Jaffe-Campanacci syndrome
Renal / Electrolyte Chronic renal failure, nephrotic syndrome
Rheum / Immune / Allergy Churg-Strauss syndrome, sarcoidosis, Sjogren's syndrome, systemic lupus erythematosus, Dressler's syndrome, rheumatoid arthritis, lupus pleuritis
Sexual Jaffe-Campanacci syndrome
Trauma Chest trauma
Urologic No underlying causes
Dental No underlying causes
Miscellaneous Hypoproteinemia, radiation

Causes in Alphabetical Order

References

  1. ↑ 1.0 1.1 Chawla RK, Madan A, Chawla A, Arora HN, Chawla K (2015). "Bilateral Pleural Effusion: A Rare Case Report". Indian J Chest Dis Allied Sci. 57 (4): 243–5. PMID 27164734.
  2. ↑ 2.0 2.1 Gilbert CR, Yarmus LB, Feller-Kopman DJ, Lee HJ, Gorden JA (2016). "The Undefined Value of Pleural Interventions in Advanced Heart Failure and Recurrent Pleural Effusions". Ann Am Thorac Soc. 13 (3): 447–8. doi:10.1513/AnnalsATS.201512-825LE. PMID 26963358.
  3. ↑ 3.0 3.1 Riccio E, Argentino G, Pisani A, Memoli B (2013). "Pleural effusion in peritoneal dialysis: overload or leakage?". Clin Exp Nephrol. 17 (6): 907. doi:10.1007/s10157-013-0794-8. PMID 23494296.
  4. ↑ 4.0 4.1 Shah S, Robson N, Sajid S (2015). "Pleuro-Peritoneal Fistula – An Important Condition to Consider in Patients using Peritoneal Dialysis". Acute Med. 14 (2): 69–71. PMID 26305084.
  5. ↑ 5.0 5.1 Asim M, Hamid EM (2013). "Pleuroperitoneal leak in a peritoneal dialysis patient". BMJ Case Rep. 2013. doi:10.1136/bcr-2013-200130. PMC 3736585. PMID 23853026.
  6. ↑ 6.0 6.1 Lee J, Lim JK, Lee SY, Yoo SS, Lee SY, Cha SI; et al. (2016). "Neutrophilic Loculated Tuberculous Pleural Effusion: Incidence, Characteristics and Differentiation From Complicated Parapneumonic Effusion". Am J Med Sci. 351 (2): 153–9. doi:10.1016/j.amjms.2015.11.010. PMID 26897270.
  7. ↑ Butani L, Polinsky MS, Kaiser BA, Baluarte HJ (1998). "Pleural effusion complicating acute peritoneal dialysis in hemolytic uremic syndrome". Pediatr Nephrol. 12 (9): 772–4. PMID 9874325.
  8. ↑ Hanna J, Truemper E, Burton E (1997). "Superior vena cava thrombosis and chylothorax: relationship in pediatric nephrotic syndrome". Pediatr Nephrol. 11 (1): 20–2. PMID 9035166.
  9. ↑ Jenkins PG, Shelp WD (1974). "Recurrent pleural transudate in the nephrotic syndrome. A new approach to treatment". JAMA. 230 (4): 587–8. PMID 4479274.
  10. ↑ Wang Z, Xia G, Lan L, Liu F, Wang Y, Liu B; et al. (2016). "Pleural Effusion in Multiple Myeloma". Intern Med. 55 (4): 339–45. doi:10.2169/internalmedicine.55.4733. PMID 26875957.
  11. ↑ Light, Richard J. (2007). Pleural diseases. Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-6957-4.
  12. ↑ 12.0 12.1 Murray HG, Stone PR, Strand L, Flower J (1993). "Fetal pleural effusion following maternal indomethacin therapy". Br J Obstet Gynaecol. 100 (3): 277–9. PMID 8476835.
  13. ↑ Bartlett RP, Greipp PR, Tefferi A, Cupps RE, Mullan BP, Trastek VF (1995). "Extramedullary hematopoiesis manifesting as a symptomatic pleural effusion". Mayo Clin Proc. 70 (12): 1161–4. doi:10.1016/S0025-6196(11)63442-3. PMID 7490917.

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