[PMC free article] [PubMed] [Google Scholar] 6

[PMC free article] [PubMed] [Google Scholar] 6. the current evidence on the use of the 5-alpha reductase inhibitors finasteride and dutasteride. We also discuss fresh growing hormonal manipulation strategies for individuals with LUTS secondary to BPO. work on a rat model of BPH has also demonstrated that GHRH antagonists (JMR 132, MIA-313 and MIA 459) reduced the excess weight of the prostate of laboratory rats significantly.[27] This reduction in prostatic weight was associated with significant changes in the expression of genes related to growth factors, inflammatory cytokines and signal transduction. In addition, reduction of inflammatory proteins such as IL-1 , NF-k/p65, and cyclooxygenase-2 was also mentioned. Thus, it is postulated that GHRH antagonists lower prostatic excess weight in experimental BPH by causing direct inhibition of GHRH receptors on prostate cells. Combination therapy using GnRH and GHRH antagonists SAR156497 Due to the potential tasks of GnRH and GHRH in BPH development, Rick the combined effect of GnRH and GHRH antagonists using a rat BPH model. When GnRH and GHRH antagonists were used in combination, it resulted in a further 10% reduction of prostatic volume compared with using either of these agents on its own. Thus, combination therapy of GnRH and GHRH antagonists may emerge like a novel treatment strategy for men suffering from LUTS due to BPO in the future. Summary Current hormonal treatment of male LUTS is limited to the use of 5-alpha reductase inhibitors. These have been shown to improve urinary symptoms and to reduce the risk of disease progression. A number of fresh hormonal treatments are currently becoming investigated such as GnRH and GHRH antagonists. Although preliminary work has yielded fascinating results, so much the vast majority of these have been small and non-randomized studies. Thus, further high quality, multi-center, double-blind randomized controlled tests are urgently required before the true clinical utility of these novel hormonal treatment modalities can be fully established. Footnotes Source of Support: Nil Discord of Interest: None declared. Referrals 1. Ventura S, Oliver Vl, White colored CW, Xie JH, Haynes JM, Exintaris B. Novel drug focuses on for the pharmacotherapy of benign prostatic hyperplasia. Br J Pharmacol. 2011;163:891C907. [PMC free article] [PubMed] [Google Scholar] 2. Oelke M, Bachmann A, Descazeaud A, Emberton M, Gravas S, Michel MC, et al. EAU recommendations on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction. Eur Urol. 2013;64:118C40. [PubMed] [Google Scholar] 3. Nicholson TM, Ricke WA. Androgens and estrogens in benign prostatic hyperplasia: Recent, present and future. Differentiation. 2011;82:184C99. [PMC free article] [PubMed] [Google Scholar] 4. Dmochowski RR. Bladder store obstruction: Etiology and evaluation. Rev Urol. 2005;7(Suppl 6):S3C13. [PMC free article] [PubMed] [Google Scholar] 5. Dawson C, Whitfield H. ABC of urology. Bladder outflow obstruction. BMJ. 1996;312:767C70. [PMC free article] [PubMed] [Google Scholar] 6. Barry MJ, Fowler FJ, Jr, OLeary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, et al. The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association. J Urol. 1992;148:1549C57. [PubMed] [Google Scholar] 7. Aragon-Ching JB, Williams KM, Gulley JL. Impact of androgen-deprivation therapy around the immune system: Implications for combination therapy of prostate malignancy. Front Biosci. 2007;12:4957C71. [PubMed] [Google Scholar] 8. Azzouni F, Godoy A, Li Y, Mohler J. The 5 alpha-reductase isozyme family: A review of basic biology and their role in human diseases. Adv Urol 2012. 2012:1C18. 530121. [PMC free article] [PubMed] [Google Scholar] 9. Tanagho F, McAninch J, editors. Smith’s General Urology. 17th ed. New York: McGraw-Hill Medical; 2008. [Google Scholar] 10. Schwinn DA, Roehrborn CG. Alpha1-adrenoceptor subtypes and lower urinary tract symptoms. Int J Urol. 2008;15:193C9. [PMC free article] [PubMed] [Google Scholar] 11. Lepor H, Kazzazi A, Djavan B. -Blockers for benign prostatic hyperplasia: The new era. Curr Opin Urol. 2012;22:7C15. [PubMed] [Google Scholar] 12. McConnell JD. Androgen ablation and blockade in the treatment of benign prostatic hyperplasia. Urol Clin North Am. 1990;17:661C70. [PubMed] [Google Scholar] 13. Guess HA, Heyse JF, Gormley GJ. The effect of finasteride on prostate-specific antigen in men.Efficacy and security of luteinizing hormone-releasing hormone antagonist cetrorelix in the treatment of symptomatic benign prostatic hyperplasia. this article, we review the current evidence on the use of the 5-alpha reductase inhibitors finasteride and dutasteride. We also discuss new emerging hormonal manipulation strategies for patients with LUTS secondary to BPO. work on a rat model of BPH has also shown that GHRH antagonists (JMR 132, MIA-313 and MIA 459) reduced the excess weight of the prostate of laboratory rats significantly.[27] This reduction in prostatic weight was associated with significant changes in the expression of genes related to growth factors, inflammatory cytokines and signal transduction. In addition, reduction of inflammatory proteins such as IL-1 , NF-k/p65, and cyclooxygenase-2 was also noted. Thus, it is postulated that GHRH antagonists lower prostatic excess weight in experimental BPH by causing direct inhibition of GHRH receptors on prostate cells. Combination therapy using GnRH and GHRH antagonists Due to the potential functions of GnRH and GHRH in BPH development, Rick the combined effect of GnRH and GHRH antagonists using a rat BPH model. When GnRH and GHRH antagonists were used in combination, it resulted in a further 10% reduction of prostatic volume compared with using either of these agents on its own. Thus, combination therapy of GnRH and GHRH antagonists may emerge as a novel treatment strategy for men suffering from LUTS due to BPO in the future. CONCLUSION Current hormonal treatment of male LUTS is limited to the use of 5-alpha reductase inhibitors. These have been shown to improve urinary symptoms and to reduce the risk of disease progression. A number of new hormonal treatments are currently being investigated such as GnRH and GHRH antagonists. Although preliminary work has yielded exciting results, so far the vast majority of these have been small and non-randomized studies. Thus, further high quality, multi-center, double-blind randomized controlled trials are urgently required before the true clinical utility of these novel hormonal treatment modalities can be fully established. Footnotes Source of Support: Nil Discord of Interest: None declared. Recommendations 1. Ventura S, Oliver Vl, White CW, Xie JH, Haynes JM, Exintaris B. Novel drug targets for the pharmacotherapy of benign prostatic hyperplasia. Br J Pharmacol. 2011;163:891C907. [PMC free article] [PubMed] [Google Scholar] 2. Oelke M, Bachmann A, Descazeaud A, Emberton M, Gravas S, Michel MC, et al. EAU guidelines on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction. Eur Urol. 2013;64:118C40. [PubMed] [Google Scholar] 3. Nicholson TM, Ricke WA. Androgens and estrogens in benign prostatic hyperplasia: Recent, present and future. Differentiation. 2011;82:184C99. [PMC free article] [PubMed] [Google Scholar] 4. Dmochowski RR. Bladder store obstruction: Etiology and evaluation. Rev Urol. 2005;7(Suppl 6):S3C13. [PMC free article] [PubMed] [Google Scholar] 5. Dawson C, Whitfield H. ABC of urology. Bladder outflow obstruction. BMJ. 1996;312:767C70. [PMC free article] [PubMed] [Google Scholar] 6. Barry MJ, Fowler FJ, Jr, OLeary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, et al. The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association. J Urol. 1992;148:1549C57. [PubMed] [Google Scholar] 7. Aragon-Ching JB, Williams KM, Gulley JL. Impact of androgen-deprivation therapy around the immune system: Implications for combination therapy of prostate malignancy. Front Biosci. 2007;12:4957C71. [PubMed] [Google Scholar] 8. Azzouni F, Godoy A, Li Y, Mohler J. The 5 alpha-reductase isozyme family: A review of basic biology and their role in human diseases. Adv Urol 2012. 2012:1C18. 530121. [PMC free article] [PubMed] [Google Scholar] 9. Tanagho F, McAninch J, editors. Smith’s General Urology. 17th ed. New York: McGraw-Hill Medical; 2008. [Google Scholar] 10. Schwinn DA, Roehrborn CG. Alpha1-adrenoceptor subtypes and lower urinary tract symptoms. Int J Urol. 2008;15:193C9. [PMC free article] [PubMed] [Google Scholar] 11. Lepor H,.Medical treatment of benign prostatic hyperplasia: 5 alpha-reductase inhibitors and alpha-adrenergic antagonists. excess weight was associated with significant changes in the expression of genes related to growth factors, inflammatory cytokines and transmission transduction. In addition, reduction of inflammatory proteins such as IL-1 , NF-k/p65, and cyclooxygenase-2 was also noted. Thus, it really is postulated that GHRH antagonists lower prostatic pounds in experimental BPH by leading to immediate inhibition of GHRH receptors on prostate cells. Mixture therapy using GnRH and GHRH antagonists Because of the potential jobs of GnRH and GHRH in BPH advancement, Rick the mixed aftereffect of GnRH and GHRH antagonists utilizing a rat BPH model. When GnRH and GHRH antagonists had been used in mixture, it led to an additional 10% reduced amount of prostatic quantity weighed against using either of the agents alone. Thus, mixture therapy of GnRH and GHRH antagonists may emerge being a book treatment technique for men experiencing LUTS because of BPO in the foreseeable future. Bottom line Current hormonal treatment of male LUTS is bound to the usage of 5-alpha reductase inhibitors. These have already been proven to improve urinary symptoms also to decrease the threat of disease development. Several brand-new hormonal treatments are being investigated such as for example GnRH and GHRH antagonists. Although primary work provides yielded exciting outcomes, so far almost all these have already been little and non-randomized research. Thus, further top quality, multi-center, double-blind randomized managed studies are urgently needed before the accurate clinical utility of the book hormonal treatment modalities could be completely established. Footnotes Way to obtain Support: Nil Turmoil appealing: None announced. Sources 1. Ventura S, Oliver Vl, Light CW, Xie JH, Haynes JM, Exintaris B. Book drug goals for the pharmacotherapy of harmless prostatic hyperplasia. Br J Pharmacol. 2011;163:891C907. [PMC free of charge content] [PubMed] [Google Scholar] 2. Oelke M, Bachmann A, Descazeaud A, Emberton M, Gravas S, Michel MC, et al. EAU suggestions on the procedure and follow-up of non-neurogenic male lower urinary system symptoms including harmless prostatic blockage. Eur Urol. 2013;64:118C40. [PubMed] [Google Scholar] 3. Nicholson TM, Ricke WA. Androgens and estrogens in harmless prostatic hyperplasia: History, present and upcoming. Differentiation. 2011;82:184C99. [PMC free of charge content] [PubMed] [Google Scholar] 4. Dmochowski RR. Bladder shop blockage: Etiology and evaluation. Rev Urol. 2005;7(Suppl 6):S3C13. [PMC free of charge content] [PubMed] [Google Scholar] 5. Dawson C, Whitfield H. ABC of urology. Bladder outflow blockage. BMJ. 1996;312:767C70. [PMC free of charge content] [PubMed] [Google Scholar] 6. Barry MJ, Fowler FJ, Jr, OLeary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, et al. The American Urological Association indicator index for harmless prostatic hyperplasia. The Dimension Committee from the American Urological Association. J Urol. 1992;148:1549C57. [PubMed] [Google Scholar] 7. Aragon-Ching JB, Williams Kilometres, Gulley JL. Influence of androgen-deprivation therapy in the disease fighting capability: Implications for mixture therapy of prostate tumor. Entrance Biosci. 2007;12:4957C71. [PubMed] [Google Scholar] 8. Azzouni F, Godoy A, Li Y, Mohler J. The 5 alpha-reductase isozyme family members: An assessment of simple biology and their function in human illnesses. Adv Urol 2012. 2012:1C18. 530121. [PMC free of charge content] [PubMed] [Google Scholar] 9. Tanagho F, McAninch J, editors. Smith’s General Urology. 17th ed. NY: McGraw-Hill Medical; 2008. [Google Scholar] 10. Schwinn DA, Roehrborn CG. Alpha1-adrenoceptor subtypes and lower urinary system symptoms. Int J Urol. 2008;15:193C9. [PMC free of charge content] [PubMed] [Google Scholar] 11. Lepor H, Kazzazi A, Djavan B. -Blockers for harmless prostatic hyperplasia: The brand new period. Curr Opin Urol. 2012;22:7C15. [PubMed] [Google Scholar] 12. McConnell JD. Androgen ablation and blockade in the treating harmless prostatic hyperplasia. Urol Clin North Am. 1990;17:661C70. [PubMed] [Google Scholar] 13. Figure HA, Heyse JF, Gormley GJ. The result of finasteride on prostate-specific antigen in guys with harmless prostatic hyperplasia. Prostate. 1993;22:31C7. [PubMed] [Google Scholar] 14. Monda JM, Oesterling JE. Treatment of harmless prostatic hyperplasia: 5 alpha-reductase inhibitors and alpha-adrenergic antagonists. Mayo Clin Proc. 1993;68:670C9. [PubMed] [Google Scholar] 15. Schr?der FH. 5.NY: McGraw-Hill Medical; 2008. LUTS supplementary to BPO. focus on a rat style of BPH in addition has proven that GHRH antagonists (JMR 132, MIA-313 and MIA 459) decreased the pounds from the prostate of lab rats considerably.[27] This decrease in prostatic weight was connected with significant shifts in the expression of genes linked to growth factors, inflammatory cytokines and sign transduction. Furthermore, reduced amount of inflammatory proteins such as for example IL-1 , NF-k/p65, and cyclooxygenase-2 was also observed. Thus, it really is postulated that GHRH antagonists lower prostatic pounds in experimental BPH by leading to immediate inhibition of GHRH receptors on prostate cells. Mixture therapy using GnRH and GHRH antagonists Because of the potential jobs of GnRH and GHRH in BPH advancement, Rick the mixed aftereffect of GnRH and GHRH antagonists utilizing a rat BPH model. When GnRH and GHRH antagonists had been used in mixture, it led to an additional 10% reduced amount of prostatic quantity weighed against using either of the agents alone. Thus, mixture therapy of GnRH and GHRH antagonists may emerge being a book treatment technique for men experiencing LUTS because of BPO in the foreseeable future. Bottom line Current hormonal treatment of male LUTS is bound to the usage of 5-alpha reductase inhibitors. These have already been proven to improve urinary symptoms also to reduce the risk of disease progression. A number of new hormonal treatments are currently being investigated such as GnRH and GHRH antagonists. Although preliminary work has yielded exciting results, so far the vast majority of these have been small and non-randomized studies. Thus, further high quality, multi-center, double-blind randomized controlled trials are urgently required before the true clinical utility of these novel hormonal treatment modalities can be fully established. Footnotes Source of Support: Nil Conflict of Interest: None declared. REFERENCES 1. Ventura S, Oliver Vl, White CW, Xie JH, Haynes JM, Exintaris B. Novel drug targets for the pharmacotherapy of benign prostatic hyperplasia. Br J Pharmacol. 2011;163:891C907. [PMC free article] [PubMed] [Google Scholar] 2. Oelke M, Bachmann A, Descazeaud A, Emberton M, Gravas S, Michel MC, et al. EAU guidelines SAR156497 on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction. Eur Urol. 2013;64:118C40. [PubMed] [Google Scholar] 3. Nicholson TM, Ricke WA. Androgens and estrogens in benign prostatic hyperplasia: Past, present and future. Differentiation. 2011;82:184C99. [PMC free article] [PubMed] [Google Scholar] 4. Dmochowski RR. Bladder outlet obstruction: Etiology and evaluation. Rev Urol. 2005;7(Suppl 6):S3C13. [PMC free article] [PubMed] [Google Scholar] 5. Dawson C, Whitfield H. ABC of urology. Bladder outflow obstruction. BMJ. 1996;312:767C70. [PMC free article] [PubMed] [Google Scholar] 6. Barry MJ, Fowler FJ, Jr, OLeary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, et al. The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association. J Urol. 1992;148:1549C57. [PubMed] [Google Scholar] 7. Aragon-Ching JB, Williams KM, Gulley JL. Impact of androgen-deprivation therapy on the immune system: Implications for combination therapy of prostate cancer. Front Biosci. 2007;12:4957C71. [PubMed] [Google Scholar] 8. Azzouni F, Godoy A, Li Y, Mohler J. The 5 alpha-reductase isozyme family: A review of basic biology and their role in human diseases. Adv Urol 2012. 2012:1C18. 530121. [PMC free article] [PubMed] [Google Scholar] 9. Tanagho F, McAninch J, editors. Smith’s General Urology. 17th ed. New York: McGraw-Hill Medical; 2008. [Google Scholar] 10. Schwinn DA, Roehrborn CG. Alpha1-adrenoceptor subtypes and lower urinary tract symptoms. Int J Urol. 2008;15:193C9. [PMC free article] [PubMed] [Google Scholar] 11. Lepor H, Kazzazi A, Djavan B. -Blockers for benign prostatic hyperplasia: The new era. Curr Opin Urol. 2012;22:7C15. [PubMed] [Google Scholar] 12. McConnell JD. Androgen ablation and blockade in the treatment of benign prostatic hyperplasia. Urol Clin North Am. 1990;17:661C70. [PubMed] [Google Scholar] 13. Guess HA, Heyse JF, Gormley GJ. The effect of finasteride SAR156497 on prostate-specific antigen in men with benign prostatic hyperplasia. Prostate. 1993;22:31C7. [PubMed] [Google Scholar] 14. Monda JM, Oesterling JE. Medical treatment of benign prostatic hyperplasia: 5 alpha-reductase inhibitors and alpha-adrenergic antagonists. Mayo Clin Proc. 1993;68:670C9. [PubMed] [Google Scholar] 15. Schr?der FH. 5 alpha-reductase inhibitors and prostatic disease. Clin Endocrinol (Oxf) 1994;41:139C47. [PubMed] [Google Scholar] 16. McConnell JD, Bruskewitz R, Walsh P, Andriole G, Lieber M, Holtgrewe HL, et al. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group. N Engl J Med. 1998;338:557C63. [PubMed] [Google Scholar] 17. Kaplan SA, Lee JY, Meehan AG, Kusek JW MTOPS Research Group. Long-term treatment with finasteride.Schr?der FH. In this article, we review the current evidence on the use of the 5-alpha reductase inhibitors finasteride and dutasteride. We also discuss new emerging hormonal manipulation strategies for patients with LUTS secondary to BPO. work on a rat model of BPH has also shown that GHRH antagonists (JMR 132, MIA-313 and MIA 459) reduced the weight of the prostate of laboratory rats significantly.[27] This reduction in prostatic weight was associated with significant changes in the expression of genes related to growth factors, inflammatory cytokines and signal transduction. In addition, reduction of inflammatory proteins such as IL-1 , NF-k/p65, and cyclooxygenase-2 was also noted. Thus, it is postulated that GHRH antagonists lower prostatic weight in experimental BPH by causing direct inhibition of GHRH receptors on prostate cells. Combination therapy using GnRH and GHRH antagonists Due to the potential roles of GnRH and GHRH in BPH development, Rick the combined effect of GnRH and GHRH antagonists using a rat BPH model. When GnRH and GHRH antagonists were used in combination, it resulted in a further 10% reduction of prostatic volume compared with using either of these agents on its own. Thus, combination therapy of GnRH and GHRH antagonists may emerge as a novel treatment strategy for men suffering from LUTS due to BPO in the future. CONCLUSION Current hormonal treatment of male LUTS is limited to the use of 5-alpha reductase inhibitors. These have been shown to improve urinary symptoms and to reduce the risk of disease progression. A number of new hormonal treatments are currently being investigated such as GnRH and GHRH antagonists. Although preliminary work has yielded exciting results, so far the vast majority of these have been small and non-randomized studies. Thus, further high quality, multi-center, double-blind randomized controlled trials are urgently needed before the accurate clinical utility of the book hormonal treatment modalities could be completely established. Footnotes Way to obtain Support: Nil Issue appealing: None announced. Personal references 1. Ventura S, Oliver Vl, Light CW, Xie JH, Haynes JM, Exintaris B. Book drug goals for the pharmacotherapy of harmless prostatic hyperplasia. Br J Pharmacol. 2011;163:891C907. [PMC free of charge content] [PubMed] [Google Scholar] 2. Oelke M, Bachmann A, Descazeaud A, Emberton M, Gravas S, Michel MC, et al. EAU suggestions on the procedure and follow-up of non-neurogenic male lower urinary system symptoms including harmless prostatic blockage. Eur Urol. 2013;64:118C40. [PubMed] [Google Scholar] 3. Nicholson TM, Ricke WA. Androgens and estrogens in harmless prostatic hyperplasia: Former, present and upcoming. Differentiation. 2011;82:184C99. [PMC free of charge content] [PubMed] [Google Scholar] 4. Dmochowski RR. Bladder electric outlet blockage: Etiology and evaluation. Rev Urol. 2005;7(Suppl 6):S3C13. [PMC free of charge content] [PubMed] [Google Scholar] 5. Dawson C, Whitfield H. ABC of urology. Bladder outflow blockage. BMJ. 1996;312:767C70. [PMC free of charge content] [PubMed] [Google Scholar] 6. Barry MJ, Fowler FJ, Jr, OLeary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, et al. The American Urological Association indicator index for harmless prostatic hyperplasia. Oaz1 The Dimension Committee from the American Urological Association. J Urol. 1992;148:1549C57. [PubMed] [Google Scholar] 7. Aragon-Ching JB, Williams Kilometres, Gulley JL. Influence of androgen-deprivation therapy over the disease fighting capability: Implications for mixture therapy of prostate cancers. Entrance Biosci. 2007;12:4957C71. [PubMed] [Google Scholar] 8. Azzouni F, Godoy A, Li Y, Mohler J. The 5 alpha-reductase isozyme family members: An assessment of simple biology and their function in human illnesses. Adv Urol 2012. 2012:1C18. 530121. [PMC free of charge content] [PubMed] [Google Scholar] 9. Tanagho F, McAninch J, editors. Smith’s General Urology. 17th ed. NY: McGraw-Hill Medical; 2008. [Google Scholar] 10. Schwinn DA, Roehrborn CG. Alpha1-adrenoceptor subtypes and lower urinary system symptoms. Int J Urol. 2008;15:193C9. [PMC free of charge content] [PubMed] [Google Scholar] 11. Lepor H, Kazzazi A, Djavan B. -Blockers for harmless prostatic hyperplasia: The brand new period. Curr Opin Urol. 2012;22:7C15. [PubMed] [Google Scholar] 12. McConnell JD. Androgen ablation and blockade in the treating harmless prostatic hyperplasia. Urol Clin North Am. 1990;17:661C70. [PubMed] [Google Scholar] 13. Figure HA, Heyse JF, Gormley GJ. The result of finasteride on prostate-specific antigen in guys with harmless prostatic hyperplasia. Prostate. 1993;22:31C7. [PubMed] [Google Scholar] 14. Monda JM, Oesterling JE. Treatment of harmless prostatic hyperplasia: 5 alpha-reductase inhibitors and alpha-adrenergic antagonists. Mayo Clin Proc. 1993;68:670C9. [PubMed] [Google Scholar] 15. Schr?der FH. 5 alpha-reductase inhibitors and prostatic disease. Clin Endocrinol (Oxf) 1994;41:139C47. [PubMed] [Google Scholar] 16. McConnell JD, Bruskewitz R, Walsh P, Andriole G, Lieber M, Holtgrewe HL, et al. The result of finasteride on the chance of severe urinary retention and the necessity for medical procedures among guys with harmless prostatic hyperplasia. Finasteride Long-Term Efficiency and Safety Research Group. N Engl J Med. 1998;338:557C63. [PubMed] [Google Scholar] 17. Kaplan SA, Lee JY, Meehan.