High density lipoprotein causes: Difference between revisions
(47 intermediate revisions by 3 users not shown) | |||
Line 2: | Line 2: | ||
{{High density lipoprotein}} | {{High density lipoprotein}} | ||
{{CMG}}; {{AE}} {{AN}}; {{RT}} | {{CMG}}; {{AE}} {{AN}}; {{RT}} | ||
==Overview== | |||
High density lipoprotein (HDL) is considered "good cholesterol" as its levels are inversely proportional to CAD. It is regarded as a positive cardiac [[risk factor]] if the levels are below 35 mg/dL or total cholesterol to HDL ratio in > 5.0 (in men) or total cholesterol to HDL ratio in > 4.5 (in women). When the levels are above 60 mg/dL it is considered a negative cardiac risk factor. | |||
==Causes== | ==Causes== | ||
===Causes of Low HDL=== | |||
* Apolipoprotein deficiency: [[Hypoalphalipoproteinemia]] can be of three types. | |||
# Impaired synthesis of apo A-I: [[Apo A-I deficiency]], Apo A-I/C-III deficiency, Apo A-I structural variants | |||
# Increased catabolism: [[Familial HDL deficiency]] or [[Tangier disease]] | |||
# Enzymatic changes: genetic, reduced activity of [[lipoprotein lipase]], elevated liver triglyceride lipase activity, [[Lecithin cholesterol acyltransferase deficiency|LCAT (lecithin cholesterol acyltransferase) deficiency]] | |||
* [[Insulin resistance]]<ref name="pmid23546765">{{cite journal |author=Filippatos TD, Rizos EC, Tsimihodimos V, Gazi IF, Tselepis AD, Elisaf MS |title=Small High-Density Lipoprotein (HDL) Subclasses are Increased with Decreased Activity of HDL-Associated Phospholipase A2 in Subjects with Prediabetes |journal=[[Lipids]] |volume= |issue= |pages= |year=2013 |month=April |pmid=23546765 |doi=10.1007/s11745-013-3787-1 |url=}}</ref><ref name="pmid23565456">{{cite journal |author=Sanyal D, Ghosh S, Mukherjee P, Mukherjee S, Chowdhury S |title=Dyslipidemia, metabolic syndrome, and liver enzymes in impaired glucose tolerance and new onset untreated, type 2 diabetes Indian subjects |journal=Indian J Endocrinol Metab |volume=16 |issue=Suppl 2 |pages=S434–5 |year=2012 |month=December |pmid=23565456 |pmc=3603104 |doi=10.4103/2230-8210.104121 |url=}}</ref> | |||
=== | * [[Diabetes mellitus]]<ref name="pmid23565456">{{cite journal |author=Sanyal D, Ghosh S, Mukherjee P, Mukherjee S, Chowdhury S |title=Dyslipidemia, metabolic syndrome, and liver enzymes in impaired glucose tolerance and new onset untreated, type 2 diabetes Indian subjects |journal=Indian J Endocrinol Metab |volume=16 |issue=Suppl 2 |pages=S434–5 |year=2012 |month=December |pmid=23565456 |pmc=3603104 |doi=10.4103/2230-8210.104121 |url=}}</ref> | ||
* Apolipoprotein deficiency: Hypoalphalipoproteinemia can be of three types. | * [[Metabolic syndrome]]<ref name="pmid23404653">{{cite journal |author=Dullaart RP, de Boer JF, Annema W, Tietge UJ |title=The inverse relation of HDL anti-oxidative functionality with serum amyloid a is lost in metabolic syndrome subjects |journal=[[Obesity (Silver Spring, Md.)]] |volume=21 |issue=2 |pages=361–6 |year=2013 |month=February |pmid=23404653 |doi=10.1002/oby.20058 |url=}}</ref><ref name="pmid23564803">{{cite journal |author=Elme A, Utriainen M, Kellokumpu-Lehtinen P, ''et al.'' |title=Obesity and physical inactivity are related to impaired physical health of breast cancer survivors |journal=Anticancer Res. |volume=33 |issue=4 |pages=1595–602 |year=2013 |month=April |pmid=23564803 |doi= |url=}}</ref> | ||
# Impaired synthesis of apo A- | |||
# Increased catabolism: [[ | |||
# Enzymatic changes: genetic, reduced activity of [[lipoprotein lipase]], elevated liver triglyceride lipase activity, LCAT (lecithin cholesterol acyltransferase) deficiency | |||
* [[Insulin resistance]] | |||
* [[Diabetes mellitus]] | |||
* [[Metabolic syndrome]] | |||
* Drugs | * Drugs | ||
# [[Beta-blocker]]s | # [[Beta-blocker]]s<ref name="pmid1353932">{{cite journal |author=Klein W |title=[Antihypertensive therapy and modification of metabolic risk factors (glucose and lipid metabolism)] |language=German |journal=Z Kardiol |volume=81 |issue=6 |pages=295–302 |year=1992 |month=June |pmid=1353932 |doi= |url=}}</ref> | ||
# [[Benzodiazepine]]s | # [[Benzodiazepine]]s | ||
# [[Anabolic steroid]]s | # [[Anabolic steroid]]s | ||
# [[Diuretic]]s | # [[Diuretic]]s | ||
# [[Progestin]]s | |||
# [[Mifepristone]]<ref name="pmid22399518">{{cite journal |author=Page ST, Krauss RM, Gross C, ''et al.'' |title=Impact of mifepristone, a glucocorticoid/progesterone antagonist, on HDL cholesterol, HDL particle concentration, and HDL function |journal=J. Clin. Endocrinol. Metab. |volume=97 |issue=5 |pages=1598–605 |year=2012 |month=May |pmid=22399518 |doi=10.1210/jc.2011-2813 |url=}}</ref> | |||
* Liver disease | * Liver disease | ||
* [[Menopause]] | * [[Menopause]]<ref name="pmid23531683">{{cite journal |author=Worsley R, Robinson PJ, Bell RJ, Moufarege A, Davis SR |title=Endogenous estrogen and androgen levels are not independent predictors of lipid levels in postmenopausal women |journal=Menopause |volume= |issue= |pages= |year=2013 |month=March |pmid=23531683 |doi=10.1097/GME.0b013e318279bd4a |url=}}</ref> | ||
* [[Obesity]] | * [[Obesity]]:High BMI is strongly associated with low serum HDl levels<ref name="pmid23564803">{{cite journal |author=Elme A, Utriainen M, Kellokumpu-Lehtinen P, ''et al.'' |title=Obesity and physical inactivity are related to impaired physical health of breast cancer survivors |journal=Anticancer Res. |volume=33 |issue=4 |pages=1595–602 |year=2013 |month=April |pmid=23564803 |doi= |url=}}</ref> | ||
* Puberty in males | * Puberty in males | ||
* [[Uremia]] | * [[Uremia]]<ref name="pmid23311247">{{cite journal |author=Cabarkapa V, Djerić M, Stosić Z, Sakac V, Zagorka LC, Vucković B |title=Evaluation of lipid parameters and bioindices in patients with different stages of chronic renal failure |journal=[[Vojnosanitetski Pregled. Military-medical and Pharmaceutical Review]] |volume=69 |issue=11 |pages=961–6 |year=2012 |month=November |pmid=23311247 |doi= |url=}}</ref> <ref name="pmid23443874">{{cite journal |author=Khoueiry G, Abdallah M, Saiful F, ''et al.'' |title=High-density lipoprotein in uremic patients: metabolism, impairment, and therapy |journal=Int Urol Nephrol |volume= |issue= |pages= |year=2013 |month=February |pmid=23443874 |doi=10.1007/s11255-012-0366-y |url=}}</ref> | ||
* Familial combined hypolipidemia | * Familial combined hypolipidemia<ref name="pmid22659251">{{cite journal |author=Minicocci I, Montali A, Robciuc MR, ''et al.'' |title=Mutations in the ANGPTL3 gene and familial combined hypolipidemia: a clinical and biochemical characterization |journal=J. Clin. Endocrinol. Metab. |volume=97 |issue=7 |pages=E1266–75 |year=2012 |month=July |pmid=22659251 |doi=10.1210/jc.2012-1298 |url=}}</ref> | ||
* Elevated [[CETP]] (cholesteryl ester transfer protein) activity: Polymorphism of the gene TaqIB (CETP gene) is known to be associated with variations in the plasma concentrations of CETP. A gene variant called TaqIB1 is associated with a higher CETP concentration and lower HDL-C levels in the plasma. Two other mutations that result in similar findings are A373P and R451Q. | * Elevated [[CETP]] ([[cholesteryl ester transfer protein]]) activity: Polymorphism of the gene TaqIB (CETP gene) is known to be associated with variations in the plasma concentrations of CETP. A gene variant called TaqIB1 is associated with a higher CETP concentration and lower HDL-C levels in the plasma. Two other mutations that result in similar findings are A373P and R451Q.<ref name="pmid22928361">{{cite journal |author=Pachocka LM, Włodarczyk M, Nowicka G, Kłosiewicz-Latoszek L, Wolańska D, Stolarska I |title=[CETP gene TaqIB polymorphism and plasma lipids in patients with overweight and obesity] |language=Polish |journal=Rocz Panstw Zakl Hig |volume=63 |issue=2 |pages=149–54 |year=2012 |pmid=22928361 |doi= |url=}}</ref><ref name="pmid23157875">{{cite journal |author=Rahimi Z, Nourozi-Rad R, Rahimi Z, Parsian A |title=Strong interaction between T allele of endothelial nitric oxide synthase with B1 allele of cholesteryl ester transfer protein TaqIB highly elevates the risk of coronary artery disease and type 2 diabetes mellitus |journal=Hum. Genomics |volume=6 |issue= |pages=20 |year=2012 |pmid=23157875 |pmc=3500247 |doi=10.1186/1479-7364-6-20 |url=}}</ref><ref name="pmid23129316">{{cite journal |author=Li YY, Wu XY, Xu J, Qian Y, Zhou CW, Wang B |title=Apo A5 -1131T/C, FgB -455G/A, -148C/T, and CETP TaqIB gene polymorphisms and coronary artery disease in the Chinese population: a meta-analysis of 15,055 subjects |journal=Mol. Biol. Rep. |volume=40 |issue=2 |pages=1997–2014 |year=2013 |month=February |pmid=23129316 |doi=10.1007/s11033-012-2257-9 |url=}}</ref><ref name="pmid22854712">{{cite journal |author=Rejeb J, Omezzine A, Boumaiza I, ''et al.'' |title=Four polymorphisms of cholesteryl ester transfer protein gene and coronary stenosis in a Tunisian population |journal=J Cardiovasc Med (Hagerstown) |volume=13 |issue=9 |pages=546–53 |year=2012 |month=September |pmid=22854712 |doi=10.2459/JCM.0b013e3283569b24 |url=}}</ref> | ||
* Smoking | * [[Smoking]] | ||
* Lack of physical exercise | * Lack of physical exercise<ref name="pmid23564803">{{cite journal |author=Elme A, Utriainen M, Kellokumpu-Lehtinen P, ''et al.'' |title=Obesity and physical inactivity are related to impaired physical health of breast cancer survivors |journal=Anticancer Res. |volume=33 |issue=4 |pages=1595–602 |year=2013 |month=April |pmid=23564803 |doi= |url=}}</ref> | ||
* High carbohydrate diet | * High carbohydrate diet | ||
=== | ===Causes of High HDL=== | ||
* Drugs | * Drugs | ||
* | # [[Desogestrel and Ethinyl Estradiol]] | ||
* | # [[Niacin]] | ||
* Weight loss | # [[Fibrate]]s | ||
# [[Statin]]s | |||
* [[Chronic alcoholism]]: Alcohol consumption raises HDL cholesterol levels by possibly increasing the transport rate of [[apolipoprotein]]s A-I and A-II. [[Alcohol]] consumption of 30-40 g/day (1-3 drinks/day) or more has been shown to increase HDL-C levels.<ref name="pmid18702334">{{cite journal |author=Krawiec A, Cylwik B, Chrostek L, Supronowicz Z, Szmitkowski M |title=[The effect of chronic alcohol abuse on the lipids, lipoproteins and apolipoproteins concentrations in the sera] |language=Polish |journal=[[Polski Merkuriusz Lekarski : Organ Polskiego Towarzystwa Lekarskiego]] |volume=24 |issue=144 |pages=521–5 |year=2008 |month=June |pmid=18702334 |doi= |url=}}</ref><ref name="pmid2862791">{{cite journal |author=Dai WS, LaPorte RE, Hom DL, ''et al.'' |title=Alcohol consumption and high density lipoprotein cholesterol concentration among alcoholics |journal=Am. J. Epidemiol. |volume=122 |issue=4 |pages=620–7 |year=1985 |month=October |pmid=2862791 |doi= |url=}}</ref> | |||
* Extensive aerobic exercise | |||
* [[Alcoholic liver disease]] | |||
* [[Weight loss]]: For every 1 kg weight loss serum HDL increases by 0.35 mg/dL<ref name="pmid22135980">{{cite journal |author=Farnier M |title=[What about HDL cholesterol?] |language=French |journal=Rev Prat |volume=61 |issue=8 |pages=1117–20 |year=2011 |month=October |pmid=22135980 |doi= |url=}}</ref> | |||
* Hyperalphalipoproteinemia | |||
* Oral [[estrogen]] replacement therapy | |||
* [[CETP]] deficiency (single [[gene]] defects in 16q21)<ref name="pmid23189141">{{cite journal |author=Chantepie S, Bochem AE, Chapman MJ, Hovingh GK, Kontush A |title=High-density lipoprotein (HDL) particle subpopulations in heterozygous cholesteryl ester transfer protein (CETP) deficiency: maintenance of antioxidative activity |journal=PLoS ONE |volume=7 |issue=11 |pages=e49336 |year=2012 |pmid=23189141 |pmc=3506611 |doi=10.1371/journal.pone.0049336 |url=}}</ref><ref name="pmid22339301">{{cite journal |author=Niesor EJ, von der Mark E, Calabresi L, ''et al.'' |title=Lipid and apoprotein composition of HDL in partial or complete CETP deficiency |journal=Curr Vasc Pharmacol |volume=10 |issue=4 |pages=422–31 |year=2012 |month=July |pmid=22339301 |doi= |url=}}</ref> | |||
* Early stage [[primary biliary cirrhosis]] <ref name="pmid1568727">{{cite journal |author=Crippin JS, Lindor KD, Jorgensen R, ''et al.'' |title=Hypercholesterolemia and atherosclerosis in primary biliary cirrhosis: what is the risk? |journal=Hepatology |volume=15 |issue=5 |pages=858–62 |year=1992 |month=May |pmid=1568727 |doi= |url=}}</ref><ref name="pmid4054519">{{cite journal |author=Jahn CE, Schaefer EJ, Taam LA, ''et al.'' |title=Lipoprotein abnormalities in primary biliary cirrhosis. Association with hepatic lipase inhibition as well as altered cholesterol esterification |journal=Gastroenterology |volume=89 |issue=6 |pages=1266–78 |year=1985 |month=December |pmid=4054519 |doi= |url=}}</ref> | |||
==References== | ==References== |
Latest revision as of 15:14, 28 January 2015
High Density Lipoprotein Microchapters |
Diagnosis |
---|
Treatment |
Clinical Trials |
Case Studies |
High density lipoprotein causes On the Web |
American Roentgen Ray Society Images of High density lipoprotein causes |
Risk calculators and risk factors for High density lipoprotein causes |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]; Raviteja Guddeti, M.B.B.S. [3]
Overview
High density lipoprotein (HDL) is considered "good cholesterol" as its levels are inversely proportional to CAD. It is regarded as a positive cardiac risk factor if the levels are below 35 mg/dL or total cholesterol to HDL ratio in > 5.0 (in men) or total cholesterol to HDL ratio in > 4.5 (in women). When the levels are above 60 mg/dL it is considered a negative cardiac risk factor.
Causes
Causes of Low HDL
- Apolipoprotein deficiency: Hypoalphalipoproteinemia can be of three types.
- Impaired synthesis of apo A-I: Apo A-I deficiency, Apo A-I/C-III deficiency, Apo A-I structural variants
- Increased catabolism: Familial HDL deficiency or Tangier disease
- Enzymatic changes: genetic, reduced activity of lipoprotein lipase, elevated liver triglyceride lipase activity, LCAT (lecithin cholesterol acyltransferase) deficiency
- Liver disease
- Menopause[7]
- Obesity:High BMI is strongly associated with low serum HDl levels[4]
- Puberty in males
- Uremia[8] [9]
- Familial combined hypolipidemia[10]
- Elevated CETP (cholesteryl ester transfer protein) activity: Polymorphism of the gene TaqIB (CETP gene) is known to be associated with variations in the plasma concentrations of CETP. A gene variant called TaqIB1 is associated with a higher CETP concentration and lower HDL-C levels in the plasma. Two other mutations that result in similar findings are A373P and R451Q.[11][12][13][14]
- Smoking
- Lack of physical exercise[4]
- High carbohydrate diet
Causes of High HDL
- Drugs
- Chronic alcoholism: Alcohol consumption raises HDL cholesterol levels by possibly increasing the transport rate of apolipoproteins A-I and A-II. Alcohol consumption of 30-40 g/day (1-3 drinks/day) or more has been shown to increase HDL-C levels.[15][16]
- Extensive aerobic exercise
- Alcoholic liver disease
- Weight loss: For every 1 kg weight loss serum HDL increases by 0.35 mg/dL[17]
- Hyperalphalipoproteinemia
- Oral estrogen replacement therapy
- CETP deficiency (single gene defects in 16q21)[18][19]
- Early stage primary biliary cirrhosis [20][21]
References
- ↑ Filippatos TD, Rizos EC, Tsimihodimos V, Gazi IF, Tselepis AD, Elisaf MS (2013). "Small High-Density Lipoprotein (HDL) Subclasses are Increased with Decreased Activity of HDL-Associated Phospholipase A2 in Subjects with Prediabetes". Lipids. doi:10.1007/s11745-013-3787-1. PMID 23546765. Unknown parameter
|month=
ignored (help) - ↑ 2.0 2.1 Sanyal D, Ghosh S, Mukherjee P, Mukherjee S, Chowdhury S (2012). "Dyslipidemia, metabolic syndrome, and liver enzymes in impaired glucose tolerance and new onset untreated, type 2 diabetes Indian subjects". Indian J Endocrinol Metab. 16 (Suppl 2): S434–5. doi:10.4103/2230-8210.104121. PMC 3603104. PMID 23565456. Unknown parameter
|month=
ignored (help) - ↑ Dullaart RP, de Boer JF, Annema W, Tietge UJ (2013). "The inverse relation of HDL anti-oxidative functionality with serum amyloid a is lost in metabolic syndrome subjects". Obesity (Silver Spring, Md.). 21 (2): 361–6. doi:10.1002/oby.20058. PMID 23404653. Unknown parameter
|month=
ignored (help) - ↑ 4.0 4.1 4.2 Elme A, Utriainen M, Kellokumpu-Lehtinen P; et al. (2013). "Obesity and physical inactivity are related to impaired physical health of breast cancer survivors". Anticancer Res. 33 (4): 1595–602. PMID 23564803. Unknown parameter
|month=
ignored (help) - ↑ Klein W (1992). "[Antihypertensive therapy and modification of metabolic risk factors (glucose and lipid metabolism)]". Z Kardiol (in German). 81 (6): 295–302. PMID 1353932. Unknown parameter
|month=
ignored (help) - ↑ Page ST, Krauss RM, Gross C; et al. (2012). "Impact of mifepristone, a glucocorticoid/progesterone antagonist, on HDL cholesterol, HDL particle concentration, and HDL function". J. Clin. Endocrinol. Metab. 97 (5): 1598–605. doi:10.1210/jc.2011-2813. PMID 22399518. Unknown parameter
|month=
ignored (help) - ↑ Worsley R, Robinson PJ, Bell RJ, Moufarege A, Davis SR (2013). "Endogenous estrogen and androgen levels are not independent predictors of lipid levels in postmenopausal women". Menopause. doi:10.1097/GME.0b013e318279bd4a. PMID 23531683. Unknown parameter
|month=
ignored (help) - ↑ Cabarkapa V, Djerić M, Stosić Z, Sakac V, Zagorka LC, Vucković B (2012). "Evaluation of lipid parameters and bioindices in patients with different stages of chronic renal failure". Vojnosanitetski Pregled. Military-medical and Pharmaceutical Review. 69 (11): 961–6. PMID 23311247. Unknown parameter
|month=
ignored (help) - ↑ Khoueiry G, Abdallah M, Saiful F; et al. (2013). "High-density lipoprotein in uremic patients: metabolism, impairment, and therapy". Int Urol Nephrol. doi:10.1007/s11255-012-0366-y. PMID 23443874. Unknown parameter
|month=
ignored (help) - ↑ Minicocci I, Montali A, Robciuc MR; et al. (2012). "Mutations in the ANGPTL3 gene and familial combined hypolipidemia: a clinical and biochemical characterization". J. Clin. Endocrinol. Metab. 97 (7): E1266–75. doi:10.1210/jc.2012-1298. PMID 22659251. Unknown parameter
|month=
ignored (help) - ↑ Pachocka LM, Włodarczyk M, Nowicka G, Kłosiewicz-Latoszek L, Wolańska D, Stolarska I (2012). "[CETP gene TaqIB polymorphism and plasma lipids in patients with overweight and obesity]". Rocz Panstw Zakl Hig (in Polish). 63 (2): 149–54. PMID 22928361.
- ↑ Rahimi Z, Nourozi-Rad R, Rahimi Z, Parsian A (2012). "Strong interaction between T allele of endothelial nitric oxide synthase with B1 allele of cholesteryl ester transfer protein TaqIB highly elevates the risk of coronary artery disease and type 2 diabetes mellitus". Hum. Genomics. 6: 20. doi:10.1186/1479-7364-6-20. PMC 3500247. PMID 23157875.
- ↑ Li YY, Wu XY, Xu J, Qian Y, Zhou CW, Wang B (2013). "Apo A5 -1131T/C, FgB -455G/A, -148C/T, and CETP TaqIB gene polymorphisms and coronary artery disease in the Chinese population: a meta-analysis of 15,055 subjects". Mol. Biol. Rep. 40 (2): 1997–2014. doi:10.1007/s11033-012-2257-9. PMID 23129316. Unknown parameter
|month=
ignored (help) - ↑ Rejeb J, Omezzine A, Boumaiza I; et al. (2012). "Four polymorphisms of cholesteryl ester transfer protein gene and coronary stenosis in a Tunisian population". J Cardiovasc Med (Hagerstown). 13 (9): 546–53. doi:10.2459/JCM.0b013e3283569b24. PMID 22854712. Unknown parameter
|month=
ignored (help) - ↑ Krawiec A, Cylwik B, Chrostek L, Supronowicz Z, Szmitkowski M (2008). "[The effect of chronic alcohol abuse on the lipids, lipoproteins and apolipoproteins concentrations in the sera]". Polski Merkuriusz Lekarski : Organ Polskiego Towarzystwa Lekarskiego (in Polish). 24 (144): 521–5. PMID 18702334. Unknown parameter
|month=
ignored (help) - ↑ Dai WS, LaPorte RE, Hom DL; et al. (1985). "Alcohol consumption and high density lipoprotein cholesterol concentration among alcoholics". Am. J. Epidemiol. 122 (4): 620–7. PMID 2862791. Unknown parameter
|month=
ignored (help) - ↑ Farnier M (2011). "[What about HDL cholesterol?]". Rev Prat (in French). 61 (8): 1117–20. PMID 22135980. Unknown parameter
|month=
ignored (help) - ↑ Chantepie S, Bochem AE, Chapman MJ, Hovingh GK, Kontush A (2012). "High-density lipoprotein (HDL) particle subpopulations in heterozygous cholesteryl ester transfer protein (CETP) deficiency: maintenance of antioxidative activity". PLoS ONE. 7 (11): e49336. doi:10.1371/journal.pone.0049336. PMC 3506611. PMID 23189141.
- ↑ Niesor EJ, von der Mark E, Calabresi L; et al. (2012). "Lipid and apoprotein composition of HDL in partial or complete CETP deficiency". Curr Vasc Pharmacol. 10 (4): 422–31. PMID 22339301. Unknown parameter
|month=
ignored (help) - ↑ Crippin JS, Lindor KD, Jorgensen R; et al. (1992). "Hypercholesterolemia and atherosclerosis in primary biliary cirrhosis: what is the risk?". Hepatology. 15 (5): 858–62. PMID 1568727. Unknown parameter
|month=
ignored (help) - ↑ Jahn CE, Schaefer EJ, Taam LA; et al. (1985). "Lipoprotein abnormalities in primary biliary cirrhosis. Association with hepatic lipase inhibition as well as altered cholesterol esterification". Gastroenterology. 89 (6): 1266–78. PMID 4054519. Unknown parameter
|month=
ignored (help)