Web site: "Information
About Herbs, Botanicals and Other Products"
URL: http://www.mskcc.org/aboutherbs
© 2003 Memorial Sloar-Kettering Cancer Center
(Monograph)
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Full Text |
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Barrie Cassileth
and K. Simon Yeung
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Soy
(Glycine Max)
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| Clinical Summary |
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Derived
from the legume of the plant. Patients take soy to treat and prevent
cancer, heart disease, and menopausal symptoms. Soybeans contain various
proteins, vitamins, and minerals, as well as significant amounts of
isoflavones (e.g. genistein, daidzein, and glycitein), and are a good
source of fiber. Isoflavones are considered phytoestrogens and exhibit
both selective estrogen receptor modulator activity and non-hormonal
effects. Clinical data suggest that soy isoflavones are no more effective
than placebo for treating menopausal symptoms in patients with breast
cancer. Epidemiologic, laboratory animal, and in vitro data suggest that
soy may be used as an alternative to conventional hormone replacement
therapy to treat menopausal symptoms, but with questionable efficacy.
Other data suggest that soy may slow bone density loss and prevent breast
cancer, but clinical results are inconsistent. Evidence suggesting that
soy proteins have a protective effect against prostate cancer is primarily
epidemiologic or in vitro. It is unknown whether isoflavones influence
hormone-dependent cancers. However, one epidemiological report
suggests dietary soy can increase risk of bladder cancer. Numerous studies
indicate that soy lowers total cholesterol levels. Animal and human
studies reveal that soy protein can decrease low-density lipoprotein (LDL)
cholesterol, inhibit LDL oxidation, and possibly increase high-density
lipoprotein (HDL) cholesterol. Genistein specifically appears to increase
blood vessel flexibility.
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| Scientific Name |
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Glycine
Max
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| Also Known As |
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Soybean,
soya, Glycine soja, tofu, miso, tempeh
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| Food Sources |
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Raw
soybeans, low-fat soy flour, roasted soybeans, dry-roasted soy beans, soy
milk, tofu, and soy protein isolate. No isoflavones are contained in soy
sauce or soy oil.
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| Purported Uses |
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• Cancer
prevention
• Cardiovascular
disease
• High
cholesterol
• Menopausal
symptoms
• Osteoporosis
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Constituents
[1], [2] |
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• Isoflavones:
Genistein, daidzein, glycitein
• Glucosides
• Phospholipids:
Phosphatidylcholine, lecithin, linoleic acid, oleic acid
• Protein
• Carbohydrate
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| Mechanism Of Action [1], [2], [3], [4],
[5], [6], [7] |
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Soy
contains significant amounts of the isoflavones genistein
(4’.5,7-trihydroxyisoflavone), daidzein (4’,7-dihydroxyisoflavone),
and glycitein (4',7-dihydroxy-6-methoxyisoflavone). In
perimenopausal women, the estrogenic effects of soy isoflavones are weak
because estrogen is abundant. At menopause, it is believed that this
effect increases due to the decrease in endogenous estrogen. Animal
studies suggest that genistein and daidzein have an ability to prevent or
reduce bone loss in a manner similar to that of synthetic estrogen due to
increased beta versus alpha estrogen receptor binding. Soy may also
contribute to maintaining bone density by causing less calcium to be
excreted in the urine. Soy's capacity for osteoporosis prophylaxis is
based largely on hypotheses rather than clinical data.
Several mechanisms for the chemopreventative effects of dietary soy are
proposed. Soybeans contain at least five anticarcinogenic phytochemicals:
isoflavones, saponins, phytates, phytosterols, and protease inhibitors.
Pilot results suggest that soy isoflavones have antioxidant activity.
Genistein demonstrates antiproliferative effects in multiple cell lines
including breast cancer (estrogen receptor positive and negative),
prostate cancer, neuroblastoma, sarcoma, and retinoblastoma. Other soy
isoflavones (daidzein, etc.) demonstrate growth inhibition of breast
cancer cell lines, although the action is weaker than with genistein.
Genistein may act as an antiestrogen by competing for receptor binding,
possibly resulting in reduced estrogen-induced stimulation of breast cell
proliferation and breast tumor formation. Alternatively, soy isoflavones
may reduce breast cancer risk by decreasing endogenous ovarian steroid
levels.
Genistein and other phytoestrogens inhibit the growth of
androgen-dependent and -independent human prostate cancer cell lines.
Rather than inhibit etiologic factors, soy protein extracts appear to
influence the progression of established tumors. Other proposed mechanisms
of prostate cancer prevention include genistein-induced prostate cancer
cell adhesion, direct growth inhibition, and induction of apoptosis.
Growth inhibition appears to be independent of genistein’s estrogenic
effects.
The exact mechanism for soy’s cholesterol-lowering effect remains
unknown. Proposed mechanisms include phytoestrogen-induced hyperthyroid
state and increased excretion of bile acids, which may enhance removal of
LDL. Isoflavones also may inhibit oxidation of LDL. So far, the soundest
support is for altered hepatic metabolism with enhanced removal of LDL and
VLDL by hepatocytes.
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Pharmacokinetics
[8] |
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Absorption
Prior to absorption, isoflavones undergo extensive metabolism in the
intestinal tract. Genistein is formed from biochanin A, and daidzein from
formonentin. Genistein, daidzein, and glycitein may be metabolized further
to specific metabolites such as equol, O-desmethylangolensis,
dihydrogenistein, and p-ethylphenol. Many variables can affect this
metabolism. A 2001 analysis of 33 phytoestrogen supplements and extracts
demonstrated notable differences in isoflavone content as compared to
manufacturer claims. Qualitative and quantitative differences in plasma
concentrations of isoflavones were observed based on the type of
supplement used. Such variations in pharmacokinetics and metabolism should
be taken into consideration when conducting clinical studies.
Metabolism/Excretion
Following absorption, isoflavones undergo enterohepatic circulation, are
secreted into bile, and are eliminated via the kidneys primarily as
glucuronide conjugates. However, a portion of isoflavones in the portal
blood can escape first-pass liver uptake, entering peripheral circulation.
The plasma half-life of genistein and daidzein is approximately 8 hours.
In adults, peak concentrations occur in 6 to 8 hours.
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Contraindications
[9] |
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Soy
is contraindicated in patients who are hypersensitive to soy products.
There is an ongoing debate as to whether soy should be contraindicated in
those with estrogen-dependent tumors.
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| Adverse Reactions |
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Reported:
Flatulence, allergic reactions.
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Drug Interactions
[10] |
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Tamoxifen:
Animal studies suggest that genistein, a soy isoflavone, may antagonize
the effects of tamoxifen on estrogen-dependent breast cancer (MCF-7).
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| Literature Summary And Critique |
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Sun
CL, et al. Dietary
Soy and Increased Risk of Bladder Cancer: the Singapore Chinese Health
Study.Cancer
Epidemiol Biomarkers Prev.
2002 Dec;11(12):1674-1677.
In
this epidemiological report, 329,848 person-years of follow-up were
accrued in a Singapore Chinese Health Study. Sixty-one confirmed cases
were identified. Increase in dietary soy was positively associated with
elevated bladder cancer risk. This risk was similar between men and women
and was not explained by other dietary factors.
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Van
Patten CL, et al. Effect of soy phytoestrogens on hot flashes in
postmenopausal women with breast cancer: a randomized, controlled clinical
trial. J
Clin Onco
2002;20:1449-55.
A prospective, randomized, double-blind evaluation of soy milk containing
90 mg isoflavones on post-menopausal breast cancer patients 4 months
status post treatment experiencing hot flashes. Patients consumed 250 ml
of soy milk (n=59) or placebo rice milk (n=64) twice daily for 12 weeks.
The study allowed patients to take prescription medications and
complementary therapies for hot flashes, provided the dose was stable for
greater than or equal to four months. Primary outcome was number of hot
flashes as recorded by patients in a daily menopause diary. Of 157
randomized patients, 9 were ineligible after randomization for reasons
unknown, and 25 dropped out for various reasons including 10 patients
intolerant to study drug (soy n=7, placebo n=3). Both the active and
placebo group demonstrated a reduction in number of hot flashes per day,
54% and 58% respectively. Adverse events were primarily gastrointestinal
in nature, including abdominal bloating and flatulence. The authors
suggest that soy milk delivering 90 mg per day isoflavones is no more
effective than placebo for the management of hot flashes experienced by
post-menopausal breast cancer patients. |
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Han
KK, et al. Benefits
of soy isoflavone therapeutic regimen on menopausal symptoms. Obstet
Gynecol
2002;99:389-94.
This double-blind, placebo-controlled study evaluated the change in
menopausal symptoms, endogenous hormone levels, and cardiovascular risk
factors in response to four months of daily 100 mg soy isoflavone. Eighty
postmenopausal women (aged 45-55) were randomized to receive either the
isoflavone (n=40) or placebo treatment (n=40) daily. The isoflavone
capsules were composed of soy protein 50.3 mg (60%), and isoflavone 33.3
mg (40%); each contained 23.3 mg of genistein, 6.2 mg of daidzein, and 3.8
mg of glycitein. Changes in menopausal symptoms were assessed at baseline
and after 4 months of treatment by means of the menopausal Kupperman
index, a numerical conversion index that evaluates 11 menopausal symptoms
including hot flashes (vasomotor), paresthesia, insomnia, and headache.
Endogenous hormone levels (FSH, LH, and 17beta-estradiol) were measured at
the same visits. Menopausal symptoms of women using isoflavone were
significantly lower during treatment than at baseline and as compared to
women taking a placebo. Similarly, while the isoflavone treatment did not
appear to alter blood pressure, plasma glucose, or high-density
lipoprotein or triglyceride levels, it did result in a significant
decrease in total cholesterol and low-density lipoprotein as compared with
baseline and with the placebo group. Estrogen levels rose with isoflavone
treatment, but transvaginal sonography studies identified no significant
increase in endometrial thickness. The soy isoflavone regime at the dosage
used appears to be a safe and effective option for postmenopausal
symptoms, with the added feature of providing potential cardiovascular
system benefits at the same time. |
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Potter
SM, et al. Soy
protein and isoflavones: their effects on blood lipids and bone density in
postmenopausal women. Am
J Clin Nutr
1998;68(suppl):1375S-9S.
A double-blind, parallel-group study conducted over a 6-month period in 66
postmenopausal women to examine the effect on blood lipids and bone
density of soy protein (40 g/d) containing varying concentrations of
isoflavones. Participants were hypercholesterolemic and living freely in
the community. A 14-day control period in which participants followed a
National Cholesterol Education Program Step 1 low-fat, low-cholesterol
diet was followed by a 6-month period in which subjects were randomly
assigned to either 1) Step 1 diet with 40 g protein daily from casein and
nonfat dry milk (control) 2) Step 1 diet with 40 g protein daily from
isolated soy protein containing 1.39 mg isoflavones/g protein, or 3) Step
1 diet with 40 g protein daily from isolated soy protein containing 2.25
mg isoflavones/g protein. Significant increases were observed in bone
mineral content and density in the lumbar spine for the group taking the
higher isoflavone-containing product as compared with the control group.
No significant decreases in total cholesterol or total triacylglycerols
were observed in the subjects taking isoflavones, although HDL cholesterol
rose significantly in both groups as compared with the control group. In
sum, both the moderate- and high-concentration isoflavone dosages
decreased risk factors for cardiovascular disease, but only the higher
concentration demonstrated an ability to protect against spinal bone loss.
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Ingram
D, et al. Case-control study of phyto-oestrogens and breast cancer. Lancet
1997;350:990-94.
In this case-control study, an inverse relationship between the risk of
both premenopausal and postmenopausal breast cancer and a high intake of
phytoestrogens (as measured by the urinary excretion of two classes of
phytochemicals, lignans and isoflavonoids) was observed. Women with newly
diagnosed breast cancer who completed questionnaires and provided 72-hour
urine collection and blood samples were matched with breast cancer-free
women. The analysis consisted of 144 pairs of individually matched
subjects (by age and residential area, among other factors). A significant
reduction in breast cancer risk was observed with high excretion of both
equol and enterolactone. A reduction in risk—but not a significant
one—was observed with the excretion of other phytoestrogens.
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| References |
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[1] Huang
KC. The Pharmacology of Chinese Herbs, 2nd ed. New York: CRC
Press; 1999. |
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[2] Schulz
V, et al. Rational Phytotherapy: A Physician's Guide to Herbal Medicine, 4th
ed. New York: Springer; 2001. |
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[3] Hasler
CM, Finn SC. Soy:
just a hill of beans? J Womens Health 1998;7:519-23. |
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[4] Messina
M, Barnes S. The role of soy products in reducing risk of cancer. J
Natl Cancer Inst 1991;83:541-6. |
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[5]
Djuric
Z, et al. Effect
of soy isoflavone supplementation on markers of oxidative stress in men
and women. Cancer Lett 2001;172:1-6 |
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[6]
Lissin
LW, Cooke JP. Phytoestrogens and cardiovascular health. J Am Coll
Cardiol 2000;35:1403-10. |
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[7]
Peterson
TG, et al. The
role of metabolism in mammary epithelial cell growth inhibition by the
isoflavones genistein and biochanin A. Carcinogenesis
1996;17:1861-9. |
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[8]
Fair
WR, Fleshner NE, Heston W. Cancer of the prostate: a nutritional disease? Urology
1997;50:840-8. |
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[9]
Lichtenstein
AH. Soy protein,
isoflavones and cardiovascular disease risk. J Nutr
1998;128:1589-92.
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[10]
Ju
YH, et al. Dietary
genistein negates the inhibitory effects of tamoxifen on growth of
estrogen-dependent human breast cancer (MCF-7) cells implanted in athymic
mice. Can Res 2002;62:2474-7. |
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[11]
Setchell
KD, et al. Bioavailability of pure isoflavones in healthy humans and
analysis of commercial soy isoflavone supplements. J Nutr
2001;131:1362S-75S. |
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[12]
Hsieh
CY, et al. Estrogenic
effects of genistein on the growth of estrogen receptor-positive human
breast cancer (MCF-7) cells in vitro and in vivo. Cancer Res
1998;58:3833-8. |
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[13]
Albertazzi
P, et al. Dietary soy supplementation and phytoestrogen levels. Obstet
Gynecol 1999;94:229-31. |
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[14]
Anderson
JW, Johnstone BM, Cook-Newall ME. Meta-analysis of the effects of soy
protein intake on serum lipids. N Eng J Med 1995;333:276-82. |
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[15]
Barnes S. Speaking at a meeting of the NIH's National Cancer Institute:
"Molecular Targets for Dietary Prevention of Prostate Cancer: Soy
Products and Genistein - Dr. Stephen Barnes." June 16, 2000. |
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[16]
Barnes
S, Peterson TG, Coward L. Rationale for the use of genistein-containing
soy matrices in chemoprevention trials for breast and prostate cancer. J
Cell Biochem Suppl 1995;22:181-7. |
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[17]
Barnes
S, et al. Soy
isoflavonoids and cancer prevention. Underlying biochemical and
pharmacological issues. Adv Exp Med Biol 1996;401:87-100. |
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[18]
British Menopause Society: Isoflavones in the Management of the Menopause.
Proceedings Supplement from an Educational Meeting. London, September
2000. J British Menopause Soc 2001;7(1). |
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[19]
Cassidy
A, Bingham S, Setchell KD. Biological effects of a diet of soy protein
rich in isoflavones on the menstrual cycle of premenopausal women. Am
J Clin Nutr
1994;60:333-40. |
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[20]
Cline
JM, Hugher CL Jr. Phytochemicals for the prevention of breast and
endometrial cancer. Cancer Treat Res 1998;94:107-34. |
|
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[21]
Fournier
DB, Erdman JW Jr., Gordon GB. Soy, its components, and cancer prevention:
a review of the in vitro, animal, and human data. Cancer Epidemiol
Biomarkers Prev 1998;7:1055-65. |
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[22]
Goodman
MT, et al. Association
of soy and fiber consumption with risk of endometrial cancer. Am
J Epidemiol
1997;146:294-306. |
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[23]
Han
KK, et al. Benefits
of soy isoflavone therapeutic regimen on menopausal symptoms. Obstet
Gynecol 2002;99:389-94. |
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[24]
Horn-Ross
PL, Hoggatt KJ, Lee MM. Phytoestrogens and thyroid cancer risk: the San
Francisco bay area thyroid cancer study. Cancer Epidemiol Biomarkers
Prev 2002;11:43-9. |
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[25]
Ingram
D, et al. Case-control study of phyto-oestrogens and breast cancer. Lancet
1997;350:990-4. |
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[26]
Messina
MJ, Loprinzi CL. Soy for breast cancer survivors: a critical review of the literature. J
Nutr 2001;131:3095S-108S. |
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[27]
Messina
MJ, Persky V, Setchell KD, Barnes S. Soy intake and cancer risk: a review
of the in vitro and in vivo data. Nutr Cancer 1994;21:113-31. |
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[28]
Moyad
MA. Soy, disease prevention, and prostate cancer. Semin
Urol Oncol 1999;17:97-102. |
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[29]
Potter
SM, Baum JA, Teng H, et al. Soy
protein and isoflavones: their effects on blood lipids and bone density in
postmenopausal women. Am J Clin Nutr 1998;68:1375S-9S. |
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[30]
Scambia
G, et al. Clinical effects of a standardized soy extract in postmenopausal
women: A pilot study. J North Am Menopause Soc 2000;7:105-11. |
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[31]
Setchell
KD. Phytoestrogens: the biochemistry, physiology, and implications for
human health of soy isoflavones. Am J Clin Nutr 1998;6:1333S-46S |
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[32]
Severson
RK, et al. A
prospective study of demographics, diet, and prostate cancer among men of
Japanese ancestry in Hawaii. Cancer
Res 1989;49:1857. |
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[33]
Upmalis
DH, et al. Vasomotor
symptom relief by soy isoflavone extract tablets in postmenopausal women:
a multicenter, double-blind, randomized, placebo-controlled study. Menopause
2000;7:236-42. |
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[34]
Kumar
NB, et al. The specific role of isoflavones on estrogen metabolism in
premenopausal women. Cancer 2002;94:1166-74. |
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[35]
Van
Patten CL, et al. Effect of soy phytoestrogens on hot flashes in
postmenopausal women with breast cancer: a randomized, controlled clinical
trial. J Clin Oncol 2002;20:1449-55. |
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[36]
Sun
CL, et al. Dietary
Soy and Increased Risk of Bladder Cancer: the Singapore Chinese Health
Study. Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1674-1677.
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| Written |
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04/25/2002 |
| Updated |
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12/24/2002
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