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Journal of Clinical Endocrinology & Metabolism, Vol 76, 309-317, Copyright © 1993 by Endocrine Society

ARTICLES

Treatment of adults with growth hormone (GH) deficiency with recombinant human GH

BA Bengtsson, S Eden, L Lonn, H Kvist, A Stokland, G Lindstedt, I Bosaeus, J Tolli, L Sjostrom and OG Isaksson
Department of Medicine, Sahlgrenska Hospital, Medical Faculty, University of Goteborg, Sweden.

In a double blind, cross-over placebo-controlled trial, we studied the effects of 26 weeks of replacement therapy with recombinant human GH on body composition, metabolic parameters, and well-being in 10 patients with adult-onset GH deficiency (GHD). All patients received appropriate thyroid, adrenal, and gonadal replacement therapy. The dose of recombinant human GH was 0.25-0.5 U/kg.week (0.013-0.026 mg/kg.day) and was administered sc daily at bedtime. One patient was withdrawn from the study because of edema and atrial fibrillation. Body composition was estimated with three independent methods: computed tomography, bioelectric impedance, and total body potassium combined with total body water assessments. The Comprehensive Psychological Rating Scale and the Symptom Check List-90 were used to assess any change in psychopathology. After 26 weeks of treatment, adipose tissue (AT) mass decreased 4.7 kg (P < 0.001). Subcutaneous AT decreased by an average of 13%, whereas visceral AT was reduced by 30%. Muscle volume increased by 2.5 kg (5%; P < 0.05). According to the four-compartment model derived from assessments of total body potassium and total body water, body cell mass and extracellular fluid volume increased significantly by 1.6 and 3.0 kg, whereas body fat decreased by 6.1 kg. Results obtained by the bioelectric impedance technique were similar. The mean (+/- SD) concentrations of insulin-like growth factor-I increased from 0.26 (0.06) at baseline to 2.56 (1.55) and 2.09 (1.03) kU/L after 6 and 26 weeks of treatment. Calcium and serum phosphate, osteocalcin, and procollagen-III concentrations were significantly higher, and intact PTH concentrations were reduced after 6 and 26 weeks of treatment, respectively. Total and free T3 concentrations were significantly increased after 6 and 26 weeks of treatment, whereas free T4 concentrations were reduced at 6 weeks, but after 26 weeks, free T4 concentrations had returned to pretreatment values. Finally, after 26 weeks of treatment, there was a decrease in the Comprehensive Psychological Rating Scale score (P < 0.05). The results show that GH replacement in GHD adults results in marked alterations in body composition, fat distribution, and bone and mineral metabolism and reduces psychiatric symptoms. Finally, we conclude that the observed beneficial effects of replacement therapy with GH are of sufficient magnitude to consider treatment of GHD adults.


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J. Gibney, M. L. Healy, M. Stolinski, S. B. Bowes, C. Pentecost, L. Breen, C. McMillan, D. L. Russell-Jones, P. H. Sonksen, and A. M. Umpleby
Effect of Growth Hormone (GH) on Glycerol and Free Fatty Acid Metabolism during Exhaustive Exercise in GH-Deficient Adults
J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1792 - 1797.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
L. Gianotti, S. Pivetti, F. Lanfranco, F. Tassone, F. Navone, E. Vittori, R. Rossetto, C. Gauna, S. Destefanis, S. Grottoli, et al.
Concomitant Impairment of Growth Hormone Secretion and Peripheral Sensitivity in Obese Patients with Obstructive Sleep Apnea Syndrome
J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 5052 - 5057.
[Abstract] [Full Text] [PDF]

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 DTBHome page
Why start an adult on growth hormone?
DTB, October 1, 2002; 40(10): 75 - 78.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
D. M. Cook, B. M. K. Biller, M. L. Vance, A. R. Hoffman, L. S. Phillips, K. M. Ford, D. P. Benziger, A. Illeperuma, S. L. Blethen, K. M. Attie, et al.
The Pharmacokinetic and Pharmacodynamic Characteristics of a Long-Acting Growth Hormone (GH) Preparation (Nutropin Depot) in GH-Deficient Adults
J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4508 - 4514.
[Abstract] [Full Text] [PDF]

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 ANN INTERN MEDHome page
W. L. Isley
Growth Hormone Therapy for Adults: Not Ready for Prime Time?
Ann Intern Med, August 6, 2002; 137(3): 190 - 196.
[Abstract] [Full Text] [PDF]

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 ANN INTERN MEDHome page
D. M. Cook
Shouldn't Adults with Growth Hormone Deficiency Be Offered Growth Hormone Replacement Therapy?
Ann Intern Med, August 6, 2002; 137(3): 197 - 201.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
S. Ezzat, S. Fear, R.-C. Gaillard, C. Gayle, H. Landy, S. Marcovitz, T. Mattioni, S. Nussey, A. Rees, and E. Svanberg
Gender-Specific Responses of Lean Body Composition and Non-Gender-Specific Cardiac Function Improvement after GH Replacement in GH-Deficient Adults
J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2725 - 2733.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
M. Le Greves, P. Steensland, P. Le Greves, and F. Nyberg
Growth hormone induces age-dependent alteration in the expression of hippocampal growth hormone receptor and N-methyl-D-aspartate receptor subunits gene transcripts in male rats
PNAS, May 14, 2002; 99(10): 7119 - 7123.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
A. Kehely, P. C. Bates, P. Frewer, M. Birkett, W. F. Blum, P. Mamessier, S. Ezzat, K. K. Y. Ho, G. Lombardi, A. Luger, et al.
Short-Term Safety and Efficacy of Human GH Replacement Therapy in 595 Adults with GH Deficiency: A Comparison of Two Dosage Algorithms
J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 1974 - 1979.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
J. Svensson, J. Fowelin, K. Landin, B.-A. Bengtsson, and J.-O. Johansson
Effects of Seven Years of GH-Replacement Therapy on Insulin Sensitivity in GH-Deficient Adults
J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2121 - 2127.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
G. Johannsson, Y. B. Sverrisdottir, L. Ellegard, P.-A. Lundberg, and H. Herlitz
GH Increases Extracellular Volume by Stimulating Sodium Reabsorption in the Distal Nephron and Preventing Pressure Natriuresis
J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1743 - 1749.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
G. Frajese, W. M. Drake, R. A. Loureiro, J. Evanson, D. Coyte, D. F. Wood, A. B. Grossman, G. M. Besser, and J. P. Monson
Hypothalamo-Pituitary Surveillance Imaging in Hypopituitary Patients Receiving Long-Term GH Replacement Therapy
J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5172 - 5175.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
E. Hernberg-Stahl, A. Luger, R. Abs, B.-A. Bengtsson, U. Feldt-Rasmussen, P. Wilton, B. Westberg, and J. P. Monson
Healthcare Consumption Decreases in Parallel with Improvements in Quality of Life during GH Replacement in Hypopituitary Adults with GH Deficiency
J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5277 - 5281.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
E. M. McConnell, A. B. Atkinson, C. Ennis, D. R. Hadden, D. R. McCance, B. Sheridan, and P. M. Bell
The Effects on Insulin Action in Adult Hypopituitarism of Recombinant Human GH Therapy Individually Titrated for Six Months
J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5342 - 5347.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
G. Gotherstrom, J. Svensson, J. Koranyi, M. Alpsten, I. Bosaus, B.-A. Bengtsson, and G. Johannsson
A Prospective Study of 5 Years of GH Replacement Therapy in GH-Deficient Adults: Sustained Effects on Body Composition, Bone Mass, and Metabolic Indices
J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4657 - 4665.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
L. Hulthen, B.-A. Bengtsson, K. S. Sunnerhagen, L. Hallberg, G. Grimby, and G. Johannsson
GH Is Needed for the Maturation of Muscle Mass and Strength in Adolescents
J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4765 - 4770.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
M. Bohlooly-Y, B. Ola, A. Gritli-Linde, O. Brusehed, O. G. P. Isaksson, C. Ohlsson, B. Soderpalm, and J. Tornell
Enhanced Spontaneous Locomotor Activity in Bovine GH Transgenic Mice Involves Peripheral Mechanisms
Endocrinology, October 1, 2001; 142(10): 4560 - 4567.
[Abstract] [Full Text] [PDF]

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 Endocr. Rev.Home page
W. M. Drake, S. J. Howell, J. P. Monson, and S. M. Shalet
Optimizing GH Therapy in Adults and Children
Endocr. Rev., August 1, 2001; 22(4): 425 - 450.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
L. Wiren, G. Johannsson, and B.-A. Bengtsson
A Prospective Investigation of Quality of Life and Psychological Well-Being after the Discontinuation of GH Treatment in Adolescent Patients Who Had GH Deficiency during Childhood
J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3494 - 3498.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
A. M. Ahmad, R. Guzder, A. M. Wallace, J. Thomas, W. D. Fraser, and J. P. Vora
Circadian and Ultradian Rhythm and Leptin Pulsatility in Adult GH Deficiency: Effects of GH Replacement
J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3499 - 3506.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
T. Munzer, S. M. Harman, P. Hees, E. Shapiro, C. Christmas, M. F. Bellantoni, T. E. Stevens, K. G. O'Connor, K. M. Pabst, C. St. Clair, et al.
Effects of GH and/or Sex Steroid Administration on Abdominal Subcutaneous and Visceral Fat in Healthy Aged Women and Men
J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3604 - 3610.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
J. L. Clasey, A. Weltman, J. Patrie, J. Y. Weltman, S. Pezzoli, C. Bouchard, M. O. Thorner, and M. L. Hartman
Abdominal Visceral Fat and Fasting Insulin Are Important Predictors of 24-Hour GH Release Independent of Age, Gender, and Other Physiological Factors
J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3845 - 3852.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
A. L. Barkan
The "Quality of Life-Assessment of Growth Hormone Deficiency in Adults" Questionnaire: Can It Be Used to Assess Quality of Life in Hypopituitarism?
J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 1905 - 1907.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
T. Laursen, C. H. Gravholt, L. Heickendorff, J. Drustrup, A.-M. Kappelgaard, J. O. L. Jørgensen, and J. S. Christiansen
Long-Term Effects of Continuous Subcutaneous Infusion Versus Daily Subcutaneous Injections of Growth Hormone (GH) on the Insulin-Like Growth Factor System, Insulin Sensitivity, Body Composition, and Bone and Lipoprotein Metabolism in GH-Deficient Adults
J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1222 - 1228.
[Abstract] [Full Text]

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 Endocr. Rev.Home page
B. L. Wajchenberg
Subcutaneous and Visceral Adipose Tissue: Their Relation to the Metabolic Syndrome
Endocr. Rev., December 1, 2000; 21(6): 697 - 738.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
A. M. Rosenfalck, S. Maghsoudi, S. Fisker, J. O. L. Jørgensen, J. S. Christiansen, J. Hilsted, A. Vølund, and S. Madsbad
The Effect of 30 Months of Low-Dose Replacement Therapy with Recombinant Human Growth Hormone (rhGH) on Insulin and C-Peptide Kinetics, Insulin Secretion, Insulin Sensitivity, Glucose Effectiveness, and Body Composition in GH-Deficient Adults
J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4173 - 4181.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
G. Amato, G. Mazziotti, C. Di Somma, E. Lalli, G. De Felice, M. Conte, M. Rotondi, M. Pietrosante, G. Lombardi, A. Bellastella, et al.
Recombinant Growth Hormone (GH) Therapy in GH-Deficient Adults: A Long-Term Controlled Study on Daily Versus Thrice Weekly Injections
J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3720 - 3725.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
A. Chrisoulidou, S. A. Beshyah, O. Rutherford, T. J. Spinks, J. Mayet, P. Kyd, V. Anyaoku, A. Haida, B. Ariff, M. Murphy, et al.
Effects of 7 Years of Growth Hormone Replacement Therapy in Hypopituitary Adults
J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3762 - 3769.
[Abstract] [Full Text]

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 EndocrinologyHome page
N. D. Aberg, B. Carlsson, L. Rosengren, J. Oscarsson, O. G. P. Isaksson, L. Ronnback, and P. S. Eriksson
Growth Hormone Increases Connexin-43 Expression in the Cerebral Cortex and Hypothalamus
Endocrinology, October 1, 2000; 141(10): 3879 - 3886.
[Abstract] [Full Text] [PDF]

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 ANN INTERN MEDHome page
G. Sesmilo, B. M.K. Biller, J. Llevadot, D. Hayden, G. Hanson, N. Rifai, and A. Klibanski
Effects of Growth Hormone Administration on Inflammatory and Other Cardiovascular Risk Markers in Men with Growth Hormone Deficiency: A Randomized, Controlled Clinical Trial
Ann Intern Med, July 18, 2000; 133(2): 111 - 122.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
N. Vahl, A. Juul, J. O. L. Jørgensen, H. Ørskov, N. E. Skakkebæk, and Jens. S. Christiansen
Continuation of Growth Hormone (GH) Replacement in GH-Deficient Patients during Transition from Childhood to Adulthood: A Two-Year Placebo-Controlled Study
J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1874 - 1881.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
A. KAMEL, S. NORGREN, A. ELIMAM, P. DANIELSSON, and C. MARCUS
Effects of Growth Hormone Treatment in Obese Prepubertal Boys
J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1412 - 1419.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
B.-A. Bengtsson and G. Johannsson
The Treatment of Growth Hormone Deficiency in Adults
J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 933 - 937.
[Full Text]

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 J. Clin. Endocrinol. Metab.Home page
B. M. K. Biller, G. Sesmilo, H. B. A. Baum, D. Hayden, D. Schoenfeld, and A. Klibanski
Withdrawal of Long-Term Physiological Growth Hormone (GH) Administration: Differential Effects on Bone Density and Body Composition in Men with Adult-Onset GH Deficiency
J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 970 - 976.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
B. Bülow, L. Hagmar, J. Eskilsson, and E. M. Erfurth
Hypopituitary Females Have a High Incidence of Cardiovascular Morbidity and an Increased Prevalence of Cardiovascular Risk Factors
J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 574 - 584.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
M. Ottosson, P. Lönnroth, P. Björntorp, and S. Edén
Effects of Cortisol and Growth Hormone on Lipolysis in Human Adipose Tissue
J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 799 - 803.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
J. D. Wallace, R. C. Cuneo, P. A. Lundberg, T. Rosén, J. O. L. Jørgensen, S. Longobardi, N. Keay, L. Sacca, J. S. Christiansen, B.-A. Bengtsson, et al.
Responses of Markers of Bone and Collagen Turnover to Exercise, Growth Hormone (GH) Administration, and GH Withdrawal in Trained Adult Males
J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 124 - 133.
[Abstract] [Full Text]

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 Endocr. Rev.Home page
G. A. Bray and F. L. Greenway
Current and Potential Drugs for Treatment of Obesity
Endocr. Rev., December 1, 1999; 20(6): 805 - 875.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
Discontinuation of Growth Hormone (GH) Treatment: Metabolic Effects in GH-Deficient and GH-Sufficient Adolescent Patients Compared with Control Subjects
J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4516 - 4524.
[Abstract] [Full Text]

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 EndocrinologyHome page
B. Söderpalm, M. Ericson, M. Bohlooly-y, J. A. Engel, and J. Törnell
Bovine Growth Hormone Transgenic Mice Display Alterations in Locomotor Activity and Brain Monoamine Neurochemistry
Endocrinology, December 1, 1999; 140(12): 5619 - 5625.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
B.-A. Bengtsson, R. Abs, H. Bennmarker, J. P. Monson, U. Feldt-Rasmussen, E. Hernberg-Ståhl, B. Westberg, P. Wilton, and C. Wüster
The Effects of Treatment and the Individual Responsiveness to Growth Hormone (GH) Replacement Therapy in 665 GH-Deficient Adults
J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 3929 - 3935.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
A. Colao, A. Cuocolo, C. Di Somma, G. Cerbone, A. M. Della Morte, E. Nicolai, R. Lucci, M. Salvatore, and G. Lombardi
Impaired Cardiac Performance in Elderly Patients with Growth Hormone Deficiency
J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 3950 - 3955.
[Abstract] [Full Text]


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