Endocrinology and Metabolism

In Kwon Han (Han IK)

15 Articles

The Postpartum Recurrence of Graves'Disease and its Contributing Factors.: Chang Hoon Yim, Hyun Ah Choi, Seung Suk Han, Hae Sung Kim, Chang Uk Lee, Ho Yeon Chung, Ki Ok Han, Hak Chul Jang, Won Keun Park, Hyun Ku Yoon, In Kwon Han; J Korean Endocr Soc. 2002;17(2):189-196. Published online April 1, 2002

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Abstract PDF: BACKGROUND
Pregnancy affects the course of Graves' Disease (GD), and patients who initially maintain euthyroid function into their middle trimester with minimum doses of antithyroid drugs become exacerbated after delivery. Even patients who are completely cured, requiring no treatment during pregnancy, can relapse after delivery. In this study, we examined the postpartum changes in the thyroid functions of patients with GD, and attempted to determine the factors contributing to these changes. METHODS: The study subjects were recruited from pregnant women visiting our outpatient clinic for routine prenatal evaluations. 45 women previously diagnosed with GD, who had been treated and cured with hyperthyroidism, and were no longer taking any thyroid medications, were evaluated for 1 year post delivery. RESULTS: Among 45 patients, 20 (44.4%) developed thyroid disorders following delivery. Postpartum thyroiditis (PPT) developed in 8 patients (17.8%), and GD developed in 12 (26.0%). The onset of the PPT disease 3.1 +/- 1.4 months following delivery, which was significantly earlier than the 6.7 +/- 2.7 months required for the post delivery onset of GD (p=0.003). The TBII values, measured during the thyrotoxic state in each womaen, were negative in women with PPT and positive in 71.4% of women with GD (p=0.030). The duration of treatment for hyperthyroidism prior or pregnancy, the number of recurrences, and the time interval without treatment, were not associated with the development of postpartum thyroid disorders. Whereas, the mean number of past pregnancies for women who developed PPT was 3.9 +/- 2.1, and was significantly higher than the 2.2+/- 1.7 for women developing no thyroid dysfunctions (p=0.044). In 13 women their initial onset of GD occurred within one year postpartum, 7 (53.8%) having had a recurrence, which was significantly higher than in women whose disease onset occurred unrelated to delivery (5 of 32 women: 15.6%). CONCLUSION: Women with GD developed postpartum thyroid dysfunctions in 44.4% of cases. Women whose initial disease onset occurred within one year postpartum had higher recurrences of GD, and women who developed PPT had a history of higher gravidity compared to the euthyroid women postpartum. Therefore, if women with GD develop postpartum thyroid dysfunctions, the diagnosis should be made, and a treatment modality planned, following careful considerations of the patients' past obstetric history, changes in clinical manifestations and the TBII values.

Prevalence of Thyroid Nodules detected by Ultrasonography in Womens Attending Health Check-Ups.: Chang Hoon Yim, Han Jin Oh, Ho Yeon Chung, Ki Ok Han, Hak Chul Jang, Hyun Ku Yoon, In Kwon Han, Byoung Hee Han, Kyung Sang Lee, Byung Jae Cho; J Korean Endocr Soc. 2002;17(2):183-188. Published online April 1, 2002

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Abstract PDF: BACKGROUND
Thyroid nodules are commonly found in clinical practice, and the recent development of thyroid ultrasonography has allowed for the detection of small nodules previously undetectable by routine palpations. Since previous studies on thyroid ultrasonography have been focused on patients with known thyroid disorders, we aimed to determine the prevalence of thyroid nodules in a female population. METHODS: We studied women in the age range 30 to 70 years visiting the health promotion center at Samsung Cheil Hospital for routine health check-ups. After excluding patients with previous thyroid disorders, 1300 women where selected to undergo thyroid ultrasonography for the detection of the presence of thyroid nodules. If nodules were found, their size and numbers were recorded, and these data correlated with the patients age. RESULTS: Of the 1300 subjects, thyroid nodules were detected in 490 (37.7%) with their prevalence (p=0.009), and that of multinodularity of thyroid nodules (p=0.001), increasing with the increasing age of the patients (Age 30 to 39: 30.8%, 40 to 49: 37.0%, 50 to 59: 41.5% and 60 to 69: 65.2%). Among these study subjects, nodules larger than 15 mm in size were detected in 29 and after performing fine needle aspirations on 18 nodules, 17 were found to be benign, with 1 papillary carcinoma, which required a total thyroidectomy. CONCLUSION: The prevalence of thyroid nodules in our female study population was 37.7%, with their prevalence, and that of multinodularity of thyroid nodules, increasing with increased age.

Thyroid Dysfunction after Abortion.: Chang Hoon Yim, Hyun Ah Choi, Ho Yeon Chung, Ki Ok Han, Hak Chul Jang, Hyun Ku Yoon, In Kwon Han; J Korean Endocr Soc. 2001;16(2):252-259. Published online April 1, 2001

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Abstract PDF: BACKGROUND
Postpartum thyroiditis is an autoimmune thyroid dysfunction that occurs in the first year after a delivery. Although a postpartum thyroid dysfunction after a full-term pregnancy is well described, little is known about its association with an abortion. The purpose of this study was to investigate the clinical and laboratory findings in thyroid dysfunction that develops after abortion and to investigate the differences in the clinical course according to the types of abortion. METHODS: Thirty patients who were proven to have thyroid dysfunction after either spontaneous or an elective abortion were studied. We analyzed their past history, the type of abortion, their clinical features, the laboratory findings and the courses of the disease. RESULTS: Seventeen patients were hypothyroid and 13 were thyrotoxic at the time of the initial thyroid function evaluation. In the thyrotoxic group, the T3 and free T4 were significantly higher but the TSH was lower than in the hypothyroid group. The titers of antimicrosomal and antithyroglobulin antibody were not different between the two groups. In the thyrotoxic group, 3 cases showed normal values, 2 cases were hypothyroid and the remaining 8 cases were persistently thyrotoxic during the 2 months of observation. TSH receptor antibodies were absent in all of the transient thyrotoxic patients, but they were present in 83.3% of the persistent thyrotoxic patients. The clinical manifestations of the thyroid dysfunction were not different according to the type of abortion. CONCLUSION: Reproductive-age women who have an abnormal thyroid function require careful history taking with respect to their history of regarding parturition or abortion in order to evaluate the possibility of a transient thyroid dysfunction after the abortion.

The Regulation of OPG/OCIF mRNA Epression by IL-1beta in Peripheral Blood Mononuclear Cells.: In Gul Moon, Ho Yeon Chung, Chang Sun Hwang, Young Soon Kang, Mi Sun Chung, Han Jin Oh, Kyu Hong Choi, Sun Woo Kim, Eui Hyun Kim, Youn Yee Kim, Chang Hoon Yim, Ki VOk Han, Hak Chul Jang, Hyun Koo Yoon, In Kwon Han; J Korean Endocr Soc. 2000;15(2):204-213. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Osteoprotegerin(OPG) is a soluble member of the tumor necrosis factor(TNF) receptor family and inhibits osteoclastogenesis by interrupting the cell-to-cell interaction between osteoblastic/stromal cells and osteoclast progenitors. OPG is expressed in many tissues including osteoblasts and may act on bone tissues in a paracrine and/or autocrine fashion. Futhermore, many cytokines and growth factors are known to influence the regulation of OPG expression in osteoblastic/stromal cells. The aims of the present study were to examine whether or not OPG was expressed in human peripheral blood mononuclear cells(PBMCs) and to investigate the effects of IL-1beta, which were known as potent osteotropic agents, on the regulation of OPG mRNA in PBMCs. METHODS: PBMCs were isolated by centrifugation over Ficoll-Hypaque density gradients from postmenopausal women and cultured in 6-well plates containing alpha-MEM supplemented with 5% FBS. The expression of OPG mRNA in PBMCs was observed by RT-PCR in adherent and nonadherent cells on culture plates. To observe the effect of OPG expression by IL-1beta, we measured the concentration of OPG mRNA by altering the concentration and incubation time of IL-1beta. The measurement of OPG mRNA was done by semi-quantitative PCR and indicated as OPG/GAPDH. RESULTS: OPG was expressed both in cells attached to the surface of culture plates and in non-adherent cells for the incubation of peripheral blood mononuclear cells. The effect of OPG mRNA by IL-1beta tend to increase in accordance with the length of incubation time and maximizes at 12 hours of incubation time and shows 1.2-3.5 times higher than the standard level at the concentration of 0.5ng/ml. However, the increased quantity in concentration varies according to individuals.] CONCLUSION: OPG mRNA is expressed in peripheral blood mononuclear cells and known to be increased by IL-1beta.

A Case of the McCune: Albright Syndrome Associated with Activating Mutations of Stimulatory G Protein.: Phil Ho Chung, Jung Kyu Whang, Youn Yee Kim, Ji Ju Whang, Chan Moon Park, Chang Hoon Yim, Ho Yeun Chung, Ki Ok Han, Hak Chul Jang, Hyun Koo Yoon, Hun Ki Min, Sung Ran Hong, Young Soon Kang, In Gul Moon, In Kwon Han; J Korean Endocr Soc. 1999;14(4):779-785. Published online January 1, 2001

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Abstract PDF: McCune-Albright syndrome (MAS) is a sporadic disease classically including polyostotic fibrous dysplasia, cafe -au-lait spots, sexual precocity, and other hyperfunctional endocrinopathies. Recent investigations suggest an etiological role for activating embryonic somatic missense mutations in the gene for the a subunit of Gs (Gsa), the G protein that stimulates adenylyl cyclase. DNA from bone, ovary, and blood was analyzed by using polymerase chain reaction and sequenced. A embryological somatic mutation of Gsa gene encoding substitution of a Cys for Arg at amino acid 201 from cells of dysplastic bone and ovary was observed, and the distribution of mutant gene reveals mosaic pattern. We report a case of McCune-Albright syndrome with an activating mutation at codon 201 of Gsa subunit on ovary and bone tissue that was experienced recently.

Association of Estrogen Receptor Genotypes with Serum Lipids and Responsiveness of Serum Lipids to Hormonal Replacement Therapy in Korean Postmenopausal Women.: So Ra Park, Jae Eun Park, Chung Kyu Hwang, Phil Ho Jung, Chang Hoon Yim, Ho Yeon Chung, Ki Ok Han, Hyun Ku Yoon, Hak Chul Jang, In Kwon Han; J Korean Endocr Soc. 1999;14(3):553-561. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Several biologically plausible mechanisms have been proposed for estrogen-mediated caridoprotection, including estrogen-assocaited changes in lipid metabolism and endothelial function of vessel walls. These effects are thought to be mediated via estrogen receptor (ER). Relationships between ER polymorphisms and serum lipid levels were not investigated enoughly. METHODS: Three restriction fragment length polymorphisms (RFLPs) at the ER gene locus, represented as B-variant, PvuII and XbaI, and their relationship to serum lipid levels were examined in 318 postmenopausal women. Their mean age was 54.5+/-6.5 years (mean+SD). An association between ER genotypes and changes in lipid levels after 1 year of estrogen replacement therapy was also investigated in follow-up 251 women. RESULTS: The B-variant was not found in Korean women. The distribution of the PvuII and XbaI polymorphisms was as follows: PP 109 (34%), Pp 166 (52%), pp 43 (14%), and XX 204 (64%), Xx 95 (30%), xx 19 (6%). Significant relationship was found between genotypes and changes in serum total cholesterol levels after lyr estrogen replacement therapy. There was no significant relationship between ER genotypes and changes in HDL cholesterol, LDL cholesterol and triglyceride levels after estrogen therapy. CONCLUSION: These data indicate that these polymorphisms are possible predictor on lipid response to estrogen replacement therapy.

Clinical Applicability of Ultrasonometric Skin Thickness Measurement in the Diagnosis of Postmenopausal Osteoporosis: Comparison with DXA.: Young Seol Kim, In Kwon Han, Duk Ju Lee, Kwang Min Kim; J Korean Endocr Soc. 1998;13(1):60-66. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Osteoporosis is developed by progressive decrease of bone rnass from decreased collagen content of bone. Accurate measurement of bone collagen is necessary for the diagnosis of osteoporosis and it is possible by bone biopsy, however bone biopsy is not easy in clinical practice. Skin collagen is consist with type I collagen which is same type of bone collagen and progressive decrease of bone collagen is reflected by decrease of skin collagen. Since skin thickness reflect skin collagen amount, skin thickness measurement may be a useful method for the evaluation of osteoporosis. So ultrasonic skin thickness measurement was developed for the evaluation of osteoporosis. METHODS: A randomly selected 200 women aged fram 30 to 71 years old were asked to have their skin thickness measured as well as lumbar vertebral DXA(Norland, USA) bone densitometry. Except for the two women who failed to complete the study, 45(22.7%) of these women were diagnosed as normal, 74(37.4%) were osteopenic and 79(39.9%) were diagnosed as osteoporosis patients using the WHO criteria. Skin thickness was measured using 20MHz Osteoson DCIII (Minhorst, Germany) at the medial side of the upper arm. A minimal of Two scans were measured and the mean value was cakulated automatically. RESULTS: The correlation coefficient of skin thickness and age was -0.121(ns), DXA BMD(bone mineral density) and age was -0.420(P<0.01), skin thickness and DXA BMD L2-L4 was 0.181(P<0.05). Skin thickness was significantly correlated with body weight(correlation coefficient 0.254, P<0.01) and BMI(correlation coefficient 0.195, P<0.01). Furthermore, the mean and standard deviation of skin thickness in normal BMD group was 0.94+-0.021mm, osteopenic group was 0.92+-0.006mm, and osteoporotic group was 0.89+-0.018mm. There was statistically significant difference in the mean values of skin thickness between the three groups even adjusted with age and BMI(P<0.05). The mean and standard deviation of skin tbickness of healthy 20-40 year old women was 1.11+-0,023mm and their mean and standard deviation of L2-L4 mean BMD was 1.17+-0.145mg/cm2. The diagnostic predictability of skin thickness less than 1mm as the risk of osteoporosis(BMD T score less than -1.0) was evaluated. The sensitivity and the specificity of skin thickness less than 1mm being osteoporotic were 78,2% and 57.8% respectively. The positive and negative predictive value of the skin thickness less than 1mm being osteoporotic were 82.2% and 36.5% respectively. CONCLUSION: This study indicate that the skin thickaess measured with the ultrasound method show good correlatian with the bone density measured with conventional DXA at the lumbar vertebra and the skin thickness less than 1mm on the medial side of the opper arm is relatively sensitive in diagnosing osteoporosis risk in Korean women. The authors suggested that a large randomized control study to define the relationship between the skin thickness and the other determinants of bone turnover in the near future.

Serum Fluoride Level in Normal Adult Women and Changes in Serum Fluoride Level after Disodium Monofluorophosphate Administration.: Hyun Koo Yoon, Mi Sun Jung, In Kul Moon, Sang Woo Kim, Ho Yeon Chung, Ki Ok Han, Hak Chul Jang, In Kwon Han, Hun Ki Min; J Korean Endocr Soc. 1997;12(4):565-570. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Since the morning fluoride level of 10 uM is recommended for adults patients being treated for osteoporosis so far, measurement of serum fluoride level is important to detect abnormally high levels or to detect levels below the therapeutic windows. Aims of this study are to determine the normal range of serum ionic fluoride levels in Korean female adults (from 5th to 7th decade), and to evaluate the in vivo fluoride pharmacokinetics of monofluorophosphate in Korean adults. METHODS: Serum level of fluoride was measured from blood samples of 72 female subjects (age 43-69years) using an ion selective electrode. For pharrnacokinetics of monofluorophosphate-calcium (MFP-Ca), 6 subjects (age 27~45 years) were included to be withdrawn the blood hourly for the first S hours and the blood was withdrawn at 24 hours after a single dose of MFP-Ca. RESULTS: Mean level of serum fluoride was 1.64+-0.12uM in 5th, 6th, 7th decades adults, and there was no difference of serum fluoride levels among age groups. Peak serum fluoride level exhibited 5.02+-0.67pM, and returned to basal level on 24 hours after a single dose of MFP-Ca. CONCLUSION: This study shows that mean serutn fluoride of Korean female adults (from 5th to 7th decade) is not different from that of other reports, and a single dose of MFP-Ca does not cause serum fluoride levels above the recommended therapeutic windows of 5-10uM for 24 hours.

Androgens and Bone Mineral Density in Women.: In Kwon Han; J Korean Endocr Soc. 1997;12(3):346-348. Published online January 1, 2001

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Abstract PDF: No abstract available.

Non-association of Pvull and Xval Estrogen receptor Genotypes with Bone Mineral Density and Bone Markers in Korean Premenopausal Women.: Hyun Koo Yoon, Ho Yeon Chung, In Gul Moon, Chang Hoon Yim, Sang Woo Kim, Ki Ok Han, In Kwon Han, Hun Ki Min, Dong Won Suh, Dong Hee Cho, Bo Kyung Park, Jong Tae Choi; J Korean Endocr Soc. 1997;12(2):207-214. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Bone mineral density (BMD) is under strong genetic control. A recently reported case of severe estrogen resistance caused by a germ-line mutation at the estrogen receptor gene locus suggests the possibility that other variants of the estrogen receptor (ER) gene could be responsible for the heritable components of bone density. METHODS: Two restriction fragment length polymorphisms (RFLPs) at the ER gene locus, represented as PvuII and XbaI, and their relationship to bone mineral density (BMD) and bone turnover markers were examined in 95 healthy premenopausal women. Their mean age was 29 +-6.9 years (mean+-SD). RESULTS: The distribution of the PvuII and XbaI RFLPs was as follows: PP 20 (21.1%), Pp 40 (42.1%), pp 35 (36.8%), and XX 5 (5.3%), Xx 33 (34.7%), xx 57 (60.0%) (capital letters signify the absence of, and lower case letters signify the presence of the restriction site of each RFLP). There was no significant relation between ER genotypes and BMD measured at several sites such as lumbar spine (L2-4), distal forearm, and femoral neck. Also no significant genotypic differences were found in the several biochemical markers and sex hormone status. CONCLUSION: These data indicate that these polymorphisms are not predietive of bone turnover nor BMD in a sample of healthy Korean premenopausal women.

Effect of Dexamethasone and Deflazacort on the Function and Gene Expression of the Primary Cultured Human Osteoblast-Like Cells.: Hyun Koo Yoon, In Myung Yang, Sung Woon Kim, Soung Seol Kim, Young Kil Choi, Ho Yeon Chung, Young Soon Kang, In Gul Moon, Chang Hoon Yim, Sang Woo Kim, Ki Ok Han, Hak Chul Chang, In Kwon Han; J Korean Endocr Soc. 1996;11(4):479-491. Published online November 7, 2019

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Abstract PDF: Background
Chronic use of glucocorticoid is known to result in osteoporosis. Deflazacort (DFZ), a synthetic glucocorticoid, has been reported to have bone sparing properties in vivo eompared to dexamethasone(DEX). Not only the direct effect of DFZ on human osteoblast but the mechanism by which the drug spares bone remains unclear. This study, therefore, is aimed to investigate the direct effect of DFZ on the proliferation and differentiation of human osteoblast as well as on the gene expression of osteocalcin and osteoblast as well as on the gene expression of osteocalcin and growth factor produced in osteoblast. Methods: Human osteoblast-like cells were cultured from a piece of the tibia removed during selective orthopedic surgery for patients without metabolic bone diseases. The morphological iden- tification of osteoblast-like cell was performed under the light microscope after alkaline phosphatase staining. Cell proliferation rate was determined by [3H] thymidine incorporation into DNA. Cell differentiation was determined by alkaline phophatase activity. mRNA expression was quanti- tatively measured by the competitive reverse transcription-polymerase ehain reaction(RT-PCR). Results: The cultured cells demonstrated 1,25-dihydroxyvitamin D3-induced increases in alkaline phophatase activity and osteocalcin mRNA expression which are the properties of osteoblast. Twenty six percent of the cultured cells were identified as osteoblast-like cells by alkaline phophatase staining. After 24hr incubation with DEX or DFZ, the [3H) thymidine incorporation was significantly inhibited by 100nM DEX or DFL Alkaine phophatase activity was significantly increased by 100nM DEX. Osteocalcin mRNA was significantly decreased by both glueocorticoids. While DEX significantly suppressed expression of asteocalcin mRNA at 10nM and 100nM, DFZ did so only at 100nM. IGF-I mRNA was significantly decreased by 100nM DEX. Conclusion: These results suggest that the inhibitory effect of DFZ on the cell proliferation and protein synthesis is less than that of DEX, which might be responsible for the bone sparing effect of DFZ in vivo.

Study on Restriction Fragment Length Polymorphisms of Vitamin - D Receptor Gene in relation to Bone Mineral Density and Bone Markers in Pre - and Postmenopausal Korean Women.: Myung Hee Yoo, Dong Won Byun, Kyo Il Suh, Guk Bae Kim, Sang Woo Kim, Ihn Gul Moon, In Kwon Han; J Korean Endocr Soc. 1994;10(3):249-261. Published online November 6, 2019

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Abstract PDF: Osteoporosis is now a major health problem because of the increasing elderly population and related osteoporosis fractures. Recently, it has been suggested that lower bone mass with/and high bone turnover rate is considered to be important in the developing of osteoporosis, and so there has been many efforts to identify the risk factors which is considered to cause lower bone mass and high bone turnover.Osteocalcin, the most abundant noncollagenous protein in bone, is a marker of bone turnover and its synthesis is induced by calcitriol(the active form of vitamine-D) through the vitamine-D receptor(VDR) and a specific vitamine D-responsive element in the osteocalcin gene promoter. Serum concentrations of osteocalcin are under the strong genetic influences and may reflect allelic variation in VDR gene. Therefore, the present study were designed to find the relationships among the polymorphisms of Vitamine-D receptor gene, bone mineral density and bone markers. We analysed the restriction fragment length polymorphisms of VDR gene with Bsm I endonuclease enzyme in relation to bone mineral density by using DEXA(dual energy X-ray absorptiometry, QDR-2000) and bone markers, especially serum osteocalcin concentrations in 356 pre- and postmenopausal Korean women.The frequence of RFLPs of VDR gene is 3.3% in BB type, 10.1% in Bb type, 86.6% in bb type. The concentrations of osteocalcin, alkaline phosphatase, procollagen-C and urinary deoxypyridinoline/creatinine were found to be higher in postmenopausal than premenopausal women and the levels of BMD were lower in postmenopausal than premenopausal women. The BB type, which is known to have a strong genetic determinant, is less frequently encountered in Korean women and does not correlate with levels of bone markers and bone mineral density. Even though the number of women with BB type is small, we noted the mean serum level of each bone marker was greater in postmenopausal women with BB type than in premenopausal women with the same genotype.In conclusion, this may suggest a partial agreement of our data with that of Australlian group and that we have to try to find out another genotype specifically related with lower bone density in Korean women.

A Case of Subclinical Hypothyroidism Associated with Turner's Syndrome.: In Kwon Han, Jung Gil Lee, Sun Wha Lee, Seong Kyu Lee, Chan Moon Pak, Ho Yeon Chung; J Korean Endocr Soc. 1994;9(1):35-38. Published online November 6, 2019

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Abstract PDF: Recently it is known that Turner's syndrome is frequently associated with hypothyroidism. We report a case of Turner's syndrome associated with subclinical hypothyroidism. A 23-year-old female was admitted to the hospital with complaints of amenorrhea and short stature. She had a mosaicism of 45, X0/46, Xi(X_q) in the cell, cultured from the peripheral blood. The plasma thyroxine and triiodothyronine were normal and there was no clinical symptom of hypothyroidism. But the thyroid-stimulating hormone(TSH) concentration was unusually higher(184 uU/L). She has been treated with the cyclic therapy of conjugated estrogen and medroxyprogesterone, in addition to the thyroxine replacement therapy. After 2 months, the menstruation was restored and TSH was normalized.

Combined estrogen-progesterone(Divina@) treatment in postmenopausal women with special reference to serum lipoprotein patterns.: Min Seon Kim, Tae Geun Oh, Kyung Soo Ko, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee, Chang Soon Koh, Hun Ki Min, Hak Chul Jang, Yong Ki Min, In Kwon Han; J Korean Endocr Soc. 1992;7(3):267-272. Published online January 1, 2001

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Abstract PDF: No abstract available.

The effect of the combined estrogen progesteron therapy for 2 years on bone mineral density in postmenopausal women.: Yong Ki Min, Hak Chul Jang, Chee Jeong Kim, In Kwon Han; J Korean Endocr Soc. 1991;6(3):222-226. Published online January 1, 2001

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Abstract PDF: No abstract available.

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