We investigated the regulation of luteinizing hormone (LH) in the male Rufous-winged Sparrow,Aimophila carpalis, a resident of the Sonoran desert that breeds after irregular summer rains. Although the testes develop in March due to increasing photoperiod and regress in September due to decreasing photoperiod, LH does not consistently increase in the spring as in other photoperiodic birds. However, throughout the year increased plasma LH is correlated with rainfall. To investigate this rainfall-associated regulation of LH secretion, we quantified immunocytochemical labeling for gonadotropin-releasing hormone I (GnRH-I), proGnRH (the GnRH precursor), and gonadotropin-inhibitory hormone (GnIH) in the hypothalamus of free-living adult males caught before (low LH), and during (high LH) the monsoon rainy season. Compared to pre-monsoon birds, birds caught during the monsoon season had larger immunoreactive GnRH-I (GnRH-I-ir) and proGnRH-ir cell bodies, as well as fewer, less densely labeled proGnRH-ir cell bodies. Birds caught during the monsoon had fewer, less densely labeled GnIH-ir cell bodies than birds caught before the monsoon. Further, there was no GnIH-ir labeling in the median eminence on either capture dates, suggesting that GnIH is not released to the pituitary gland via the portal vein at this time of year, but there were fewer GnIH-ir fibers in the preoptic area of birds caught during the monsoon season. Our data support the hypothesis that environmental factors associated with increased rainfall during the monsoon season stimulate GnRH synthesis and release to increase LH secretion. These data also suggest that GnIH could inhibit GnRH neuronal activity prior to the monsoon season.

Ackland JF, Nikolics K, Seeburg PH, Jackson IM (1988) Molecular forms of gonadotropin-releasing hormone associated peptide (GAP): changes within the rat hypothalamus and release from hypothalamic cells in vitro. Neuroendocrinology 48:376–386.
Ball GF (1993) The neural integration of environmental information by seasonally breeding birds. Am Zool 33:185–199.
Ball GF, Hahn TP (1997) GnRH neuronal systems in birds and their relation to the control of seasonal reproduction. In: GnRH Neurons: From Gene to Behavior (Parhar I, Sakuma SY, eds), pp 325–342. Tokyo: Brain Shupan.
Benkman CW (1990) Intake rates and the timing of crossbill reproduction. Auk 107:376–386.
Benkman CW (1992) White-winged Crossbill (Loxia leucoptera). In: The Birds of North America, No. 27 (Poole A, Gill F, eds), pp 1–20, doi:10.2173/bna.27. Philadelphia, PA:Birds of North America, Inc.
Bentley GE, Audage NC, Hanspal EK, Ball GF, Hahn TP (2003a) Photoperiodic response of the hypothalamo-pituitary-gonad axis in male and female canaries, Serinus canaria. J Exp Zool A 296:143–151.
Bentley GE, Jensen JP, Kaur GJ, Wacker DW, Tsutsui K, Wingfield JC (2006a) Rapid inhibition of female sexual behavior by gonadotropin-inhibitory hormone (GnIH). Horm Behav 49:550–555.
Bentley GE, Kriegsfeld LJ, Osugi T, Ukena K, O’Brien S, Perfito N, Moore IT, Wingfield JC, Tsutsui K (2006b) Interactions of gonadotropin-releasing hormone (GnRH) and gonadotropin-inhibitory hormone (GnIH) in birds and mammals. J Exp Zool 305:807–814.
Bentley GE, Perfito N, Ukena K, Tsutsui K, Wingfield JC (2003b) Gonadotropin-inhibitory peptide in song sparrows (Melospiza melodia) in different reproductive conditions, and in house sparrows (Passer domesticus) relative to chicken-gonadotropin-releasing hormone. J Neuroendocrinol 15:794–802.
Bentley GE, Spar BD, MacDougall-Shackleton SA, Hahn TP, Ball GF (2000) Photoperiodic regulation of the reproductive axis in male zebra finches, Taeniopygia guttata. Gen Comp Endocrinol 117:449–455.
Bluhm CK, Schwabl H, Schwabl I, Perera A, Follett BK, Goldsmith AR, Gwinner E (1991) Variation in hypothalamic gonadotrophin-releasing hormone content, plasma and pituitary LH, and in-vitro testosterone release in a long-distance migratory bird, the garden warbler (Sylvia borin), under constant photoperiods. J Endocrinol 128:339–345.
Cheng MF, Peng JP, Johnson P (1998) Hypothalamic neurons preferentially respond to female nest coo stimulation: Demonstration of direct acoustic stimulation of luteinizing hormone release. J Neurosci 18:5477–5489.
Cho RN, Hahn TP, MacDougall-Shackleton S, Ball GF (1998) Seasonal variation in brain GnRH in free-living breeding and photorefractory house finches (Carpodacus mexicanus). Gen Comp Endocrinol 109:244–250.
Ciccone NA, Dunn IC, Boswell T, Tsutsui K, Ubuka T, Ukena K, Sharp PJ (2004) Gonadotrophin inhibitory hormone depresses gonadotrophin alpha and follicle-stimulating hormone beta subunit expression in the pituitary of the domestic chicken. J Neuroendocrinol 16:999–1006.
Cynx J (2001) Effects of humidity on reproductive behavior in male and female zebra finches (Taeniopygia guttata). J Comp Psychol 115:196–200.
Davis MR, Fernald RD (1990) Social-control of neuronal soma size. J Neurobiol 21:1180–1188.
Dawson A (1991) Effect of daylength on the rate of recovery of photosensitivity in male starlings (Sturnus vulgaris). J Reprod Fertil 93:521–524.
Dawson A (1999) Photoperiodic control of gonadotropin-releasing hormone secretion in seasonally breeding birds. In: Neural Regulation in the Vertebrate Endocrine System (Rao P, Kluwer P, eds), pp 141–159. New York: Academic/Plenum Pub.
Dawson A (2002) Photoperiodic control of the annual cycle in birds and comparison with mammals. Ardea 90:355–367.
Dawson A (2005) Seasonal differences in the secretion of luteinising hormone and prolactin in response to N-methyl-DL-aspartate in starlings (Sturnus vulgaris). J Neuroendocrinol 17:105–110.
Dawson A, Goldsmith AR (1997) Changes in gonadotrophin-releasing hormone (GnRH-I) in the pre-optic area and median eminence of starlings (Sturnus vulgaris) during the recovery of photosensitivity and during photostimulation. J Reprod Fertil 111:1–6.
Dawson A, King VM, Bentley GE, Ball GF (2001) Photoperiodic control of seasonality in birds. J Biol Rhythms 16:365–380.
Dawson A, Talbot RT, Dunn IC, Sharp PJ (2002) Changes in basal hypothalamic chicken gonadotropin-releasing hormone-I and vasoactive intestinal polypeptide associated with a photo-induced cycle in gonadal maturation and prolactin secretion in intact and thyroidectomized starlings (Sturnus vulgaris). J Neuroendocrinol 14:533–539.
Deviche P, Saldanha CJ, Silver R (2000) Changes in brain gonadotropin-releasing hormone- and vasoactive intestinal polypeptide-like immunoreactivity accompanying reestablishment of photosensitivity in male dark-eyed juncos (Junco hyemalis). Gen Comp Endocrinol 117:8–19.
Deviche P, Small TW (2005) Environmental control of reproduction in Sonoran Desert Aimophila sparrows. In: Functional Avian Endocrinology (Dawson A, Sharp PJ, eds), pp 153–166. Narosa Publishing House.
Deviche P, Small T, Sharp PJ, Tsutsui K (2006) Control of luteinizing hormone and testosterone secretion in a flexibly breeding male passerine, the Rufous-winged Sparrow, Aimophila carpalis. Gen Comp Endocrinol 149:226–235.
Donoghue DJ, Krueger BF, Hargis BM, Miller AM, El Halawani M (1989) Thermal stress reduces serum luteinizing hormone and bioassayable hypothalamic content of luteinizing hormone-releasing hormone in hens. Biol Reprod 41:419–424.
Douglas MW, Maddox RA, Howard K, Reyes S (1993) The Mexican Monsoon. J Climate 6:1665–1677.
Dunn IC, Sharp PJ (1999) Photo-induction of hypothalamic gonadotrophin releasing hormone-I mRNA in the domestic chicken: a role for oestrogen? J Neuroendocrinol 11:371–375.
Dunn IC, Beattie KK, Maney D, Sang HM, Talbot RT, Wilson PW, Sharp PJ (1996) Regulation of chicken gonadotropin-releasing hormone-I mRNA in incubating, nest-deprived and laying bantam hens. Neuroendocrinology 63:504–513.
Dunn IC, Chen Y, Hook C, Sharp PJ, Sang HM (1993) Characterization of the chicken preprogonadotrophin-releasing hormone-I gene. J Mol Endocrinol 11:19–29.
Dutlow CM, Rachman J, Jacobs TW, Millar RP (1992) Prepubertal increases in gonadotropin-releasing hormone mRNA, gonadotropin-releasing hormone precursor, and subsequent maturation of precursor processing in male rats. J Clin Invest 90:2496–2501.
Eda-Fujiwara H, Suzuki M, Kimura T (2003) Behavioral responses of males to estradiol-treated females in the budgerigar (Melopsittacus undulatus). J Ethol 21:23–28.
Follett BK, Maung SL (1978) Rate of testicular maturation, in relation to gonadotrophin and testosterone levels, in quail exposed to various artificial photoperiods and to natural daylengths. J Endocrinol 78:267–280.
Follett BK, Pearce-Kelly AS (1990) Photoperiodic control of the termination of reproduction in Japanese Quail (Coturnix coturnix japonica). Proc R Soc Lond B Biol Sci 242:225–230.
Follett BK, Scanes CG, Cunningham FJ (1972) A radioimmunoassay for avian luteinizing hormone. J Endocrinol 52:359–378.
Foster RG, Panzica GC, Parry DM, Viglietti-Panzica C (1988) Immunocytochemical studies on the LHRH system of the Japanese quail: influence by photoperiod and aspects of sexual differentiation. Cell Tissue Res 253:327–335.
Foster RG, Plowman G, Goldsmith A.R., Follett BK (1987) Immunohistochemical demonstration of marked changes in the LHRH system of photosensitive and photorefractory European Starlings (Sturnus vulgaris). J Endocrinol 115:211–220.
Francis RC, Jacobson B, Wingfield JC, Fernald RD (1992) Hypertrophy of gonadotropin-releasing hormone-containing neurons after castration in the teleost, Haplochromis burtoni. J Neurobiol 23:1084–1093.
Goldsmith AR, Ivings WE, Pearcekelly AS, Parry DM, Plowman G, Nicholls TJ, Follett BK (1989) Photoperiodic control of the development of the LHRH neurosecretory-system of European Starlings (Sturnus vulgaris) during puberty and the onset of photorefractoriness. J Endocrinol 122:255–268.
Hahn TP (1998) Reproductive seasonality in an opportunistic breeder, the red crossbill, Loxia curvirostra. Ecology 79:2365–2375.
Hahn TP, Ball GF (1995) Changes in brain GnRH associated with photorefractoriness in House Sparrows (Passer domesticus). Gen Comp Endocrinol 99:349–363.
Hahn TP, Boswell T, Wingfield JC, Ball GF (1997) Temporal flexibility in avian reproduction: Patterns and mechanisms. Curr Ornithol 14:39–80.
Hamner WM (1968) Photorefractory period of the House Finch. Ecology 49:211–227.
Hau M, Wikelski M, Wingfield JC (2000) Visual and nutritional food cues fine-tune timing of reproduction in a neotropical rainforest bird. J Exp Zool 286:494–504.
Kang SW, Thayananuphat A, Rozenbolm I, Millam JR, Proudman JA, El Halawani ME (2006) Expression of hypothalamic GnRH-I mRNA in the female turkey at different reproductive states and following photo-stimulation. Gen Comp Endocrinol 146:91–99.
Kawamoto K, Tanaka S, Kawano M, Hayashi T, Tsuchiya K (2000) Effects of photoperiod and ambient temperature on the gonadotropin-releasing hormone neuronal system in the gray hamster, Tscherskia triton. Neuroendocrinology 72:284–292.
Kelly MJ, Garrett J, Bosch MA, Roselli CE, Douglass J, Adelman JP, Ronnekleiv OK (1989) Effects of ovariectomy on GnRH mRNA, proGnRH and GnRH levels in the preoptic hypothalamus of the female rat. Neuroendocrinology 49:88–97.
King JC, Williams TH, Gerall AA (1974) Transformations of hypothalamic arcuate neurons. 1. Changes associated with stages of estrous-cycle. Cell Tissue Res 153:497–515.
Kriegsfeld LJ, Mei DF, Bentley GE, Ubuka T, Mason AO, Inoue K, Ukena K, Tsutsui K, Silver R (2006) Identification and characterization of a gonadotropin-inhibitory system in the brains of mammals. Proc Natl Acad Sci USA 103:2410–2415.
Kriegsfeld LJ, Ranalli NJ, Trasy AG, Nelson RJ (2001) Food restriction affects the gonadotropin releasing hormone neuronal system of male prairie voles (Microtus ochrogaster). J Neuroendocrinol 13:791–798.
Lack D (1968) Ecological Adaptations for Breeding in Birds. London: Methuen and Co.
Leitner S, Van’t Hof TJ, Gahr M (2003) Flexible reproduction in wild canaries is independent of photoperiod. Gen Comp Endocrinol 130:102–108.
Ligon JD (1974) Green cones of Pinon Pine stimulate late summer breeding in Pinon Jay. Nature 250:80–82.
Lowther PE, Groschupf KD, Russell SM (1999) Rufous-winged Sparrow (Aimophila carpalis). In: The Birds of North America, No. 422 (Poole A, Gill F, eds). pp 1–20, doi:10.2173/bna.422. Philadelphia, PA: Birds of North America, Inc.
MacDougall-Shackleton SA, Deviche P, Crain RD, Ball GF, Hahn TP (2001) Seasonal changes in brain GnRH immunoreactivity and song-control nuclei volumes in an opportunistically breeding songbird. Brain Behav Evol 58:38–48.
Martin R, Deviche P, Tsutsui K (2003) Sexually dimorphic neuroanatomical distribution of gonadotropin-inhibiting hormone in adult house finches, Carpodacus mexicanus. Program No. 611.5. Abstract Viewer/Itinerary Planner.Washington, DC: Society for Neuroscience, Online: http://sfn.scholarone.com/itin2003/main.html?new_page_id=126& abstract_id=17918&p_num=611.5&is_tech=0
Meddle SL, Bush S, Sharp PJ, Millar RP, Wingfield JC (2006) Hypothalamic pro-GnRH-GAP, GnRH-I and GnRH-II during the onset of photorefractoriness in the white-crowned sparrow (Zonotrichia leucophrys gambelii). J Neuroendocrinol 18:217–226.
Mishra MK, Tewary PD (1999) Involvement of threshold photoperiod in control of reproductive rhythmicity in migratory blackheaded bunting, Emberiza melanocephala. Chronobio Int 16:59–67.
Moore IT, Bentley GE, Wotus C, Wingfield JC (2006) Photoperiod-independent changes in immunoreactive brain gonadotropin-releasing hormone (GnRH) in a free-living, tropical bird. Brain Behav Evol 68:37–44.
Moore IT, Bonier F, Wingfield JC (2005) Reproductive asynchrony and population divergence between two tropical bird populations. Behav Ecol 16:755–762.
Moore MC (1982) Hormonal response of free-living male White-Crowned Sparrows to experimental manipulation of female sexual behavior. Horm Behav 16:323–329.
Ohmart RD (1969) Physiological and ethological adaptations of the Rufous-winged Sparrow (Aimophila carpalis) to a desert environment. Ph.D. Dissertation, University of Arizona, Tucson, Ariz.
Osugi T, Ukena K, Bentley GE, O’Brien S, Moore IT, Wingfield JC, Tsutsui K (2004) Gonadotropin-inhibitory hormone in Gambel’s white-crowned sparrow (Zonotrichia leucophrys gambelii): cDNA identification, transcript localization and functional effects in laboratory and field experiments. J Endocrinol 182:33–42.
Ottinger MA, Mobarak M, Abdelnabi M, Roth G, Proudman J, Ingram DK (2005) Effects of calorie restriction on reproductive and adrenal systems in Japanese quail: are responses similar to mammals, particularly primates? Mech Ageing Dev 126:967–975.
Panzica GC, Aste N, Castagna C, Viglietti-Panzica C, Balthazart J (2001) Steroid-induced plasticity in the sexually dimorphic vasotocinergic innervation of the avian brain: behavioral implications. Brain Res Rev 37:178–200.
Panzica GC, Plumari L, García-Ojeda E, Deviche P (1999) Central vasotocin-immunoreactive system in a male passerine bird (Junco hyemalis). J Comp Neurol 409:105–117.
Parry DM, Goldsmith AR, Millar RP, Glennie LM (1997) Immunocytochemical localization of GnRH precursor in the hypothalamus of European starlings during sexual maturation and photorefractoriness. J Neuroendocrinol 9:235–243.
Perera AD, Follett BK (1992) Photoperiodic induction in vitro: the dynamics of gonadotropin- releasing hormone release from hypothalamic explants of the Japanese quail. Endocrinology 131:2898–2908.
Pereyra ME, Sharbaugh SM, Hahn TP (2005) Interspecific variation in photo-induced GnRH plasticity among nomadic cardueline finches. Brain Behav Evol 66:35–49.
Perfito N, Bentley G, Hau M (2006) Tonic activation of brain GnRH immunoreactivity despite reduction of peripheral reproductive parameters in opportunistically breeding zebra finches. Brain Behav Evol 67:123–134.
Perfito N, Meddle SL, Tramontin AD, Sharp PJ, Wingfield JC (2005) Seasonal gonadal recrudescence in song sparrows: Response to temperature cues. Gen Comp Endocrinol 143:121–128.
Priedkalns J, Oksche A, Vleck C, Bennett RK (1984) The response of the hypothalamo-gonadal system to environmental factors in the Zebra Finch, Poephila guttata castanotis – structural and functional studies. Cell Tissue Res 238:23–35.
Pyle P (1997) Identification Guide to North American Birds. Part I. Columbidae to Ploceidae. Bolinas, CA: Slate Creek Press.
Rance NE, Mcmullen NT, Smialek JE, Price DL, Young WS (1990) Postmenopausal hypertrophy of neurons expressing the estrogen-receptor gene in the human hypothalamus. J Clin Endocrinol Metab 71:79–85.
Roberts JL, Dutlow CM, Jakubowski M, Blum M, Millar RP (1989) Estradiol stimulates preoptic area-anterior hypothalamic prognrh-gap gene-expression in ovariectomized rats. Mol Brain Res 6:127–134.
Rogers CM (1991) An evaluation of the method of estimating body fat in birds by quantifying visible subcutaneous fat. J Field Ornithol 62:349–356.
Saldanha CJ, Deviche P, Silver R (1994) Increased VIP and decreased GnRH expression in photorefractory dark-eyed juncos (Junco hyemalis). Gen Comp Endocrinol 93:128–136.
Sanchez F, Panzica GC, Viglietti-Panzica C, Aste N, Carretero J, Vazquez R (1991) A comparative-analysis of the vasotocin and vasopressin systems in the Chicken and Rat hypothalamus – An immunocytochemical study. J Hirnforsch 32:27–37.
Silverin B, Kikuchi M, Ishii S (1999) Effect of season and photoperiod on FSH in male great tits. Gen Comp Endocrinol 113:457–463.
Small TW, Sharp PJ, Deviche P (2007) Environmental regulation of the reproductive system in a flexibly breeding Sonoran Desert bird, the Rufous-winged Sparrow, Aimophila carpalis. Horm Behav 51:483–495.
Stokes TM, Leonard CM, Nottebohm F (1974) Telencephalon, diencephalon, and mesencephalon of Canary, Serinus canaria, in stereotaxic coordinates. J Comp Neurol 156:337–374.
Tsai PS, Jones JT (2005) Steroid-induced changes in the morphology of GnRH neurons in the male leopard frog, Rana pipiens: correlation with plasma gonadotropin and gonadal size. Gen Comp Endocrinol 141:152–160.
Tsuruo Y, Hisano S, Okamura Y, Tsukamoto N, Daikoku S (1984) Hypothalamic Substance-P containing neurons – sex-dependent topographical differences and ultrastructural transformations associated with stages of the estrous-cycle. Brain Res 305:331–341.
Tsutsui K, Bentley GE, Ciccone N (2005) Structure, action and functional significance of GnIH. In: Functional Avian Endocrinology (Dawson A, Sharp PJ, eds), pp 73–82. New Delhi, India: Narosa Publishing House.
Tsutsui K, Saigoh E, Ukena K, Teranishi H, Fujisawa Y, Kikuchi M, Ishii S, Sharp PJ (2000) A novel avian hypothalamic peptide inhibiting gonadotropin release. Biochem Biophys Res Comm 275:661–667.
Tsutsui K, Ubuka T, Yin H, Osugi T, Ukena K, Bentley GE, Ciccone N, Inoue K, Chowdhury VS, Sharp PJ, Wingfield JC (2006) Mode of action and functional significance of avian gonadotropin-inhibitory hormone (GnIH): A review. J Exp Zool 305:801–806.
Ubuka T, Ukena K, Sharp PJ, Bentley GE, Tsutsui K (2006) Gonadotropin-inhibitory hormone inhibits gonadal development and maintenance by decreasing gonadotropin synthesis and release in male quail. Endocrinology 147:1187–1194.
Ukena K, Ubuka T, Tsutsui K (2003) Distribution of a novel avian gonadotropin-inhibitory hormone in the quail brain. Cell Tissue Res 312:73–79.
Urbanski HF, Doan A, Pierce M (1991) Immunocytochemical investigation of luteinizing hormone-releasing hormone neurons in Syrian hamsters maintained under long or short days. Biol Reprod 44:687–692.
Viglietti-Panzica C (1986) Immunohistochemical study of the distribution of vasotocin reacting neurons in avian diencephalon. J Hirnforsch 27:559–566.
Vleck CM, Priedkalns J (1985) Reproduction in Zebra Finches – hormone levels and effect of dehydration. Condor 87:37–46.
Wada M (1993) Low-temperature and short days together induce thyroid activation and suppression of LH-release in Japanese Quail. Gen Comp Endocrinol 90:355–363.
Watson RE, Wiegand SJ, Clough RW, Hoffman GE (1986) Use of cryoprotectant to maintain long-term peptide immunoreactivity and tissue morphology. Peptides 7:155–159.
Wetsel WC, Srinivasan S (2002) Pro-GnRH processing. Prog Brain Res 141:221–241.
White SA, Fernald RD (1993) Gonadotropin-releasing-hormone containing neurons change size with reproductive state in female Haplochromis burtoni. J Neurosci 13:434–441.
White SA, Nguyen T, Fernald RD (2002) Social regulation of gonadotropin-releasing hormone. J Exp Biol 205:2567–2581.
Wilson FE (1990) On the recovery of photosensitivity in 2 passerine species, American Tree Sparrows (Spizella arborea) and Harris’ Sparrows (Zonotrichia querula). Gen Comp Endocrinol 79:283–290.
Wilson FE (1992) Photorefractory Harris’ Sparrows (Zonotrichia querula) exposed to a winter-like daylength gradually regain photosensitivity after a lag. Gen Comp Endocrinol 87:402–409.
Wingfield JC, Hahn TP, Doak D (1993) Integration of environmental factors regulating transitions of physiological states, morphology and behaviour. In: Avian Endocrinology (Sharp PJ, eds), pp 111–122. Bristol, UK: Society for Endocrinology.
Wingfield JC, Jacobs JD, Tramontin AD, Perfito N, Meddle S, Maney DL, Soma K (2000) Towards an ecological basis of hormone-behavior interactions in reproduction of birds. In: Reproduction in Context (Wallen K, Schneider JE, eds), pp 85–128. Cambridge MA: MIT Press.
Yin H, Ukena K, Ubuka T, Tsutsui K (2005) A novel G protein-coupled receptor for gonadotropin-inhibitory hormone in the Japanese quail (Coturnix japonica): identification, expression and binding activity. J Endocrinol 184:257–266.
Zann RA, Morton SR, Jones KR, Burley NT (1995) The timing of breeding by zebra finches in relation to rainfall in central Australia. Emu 95:208–222.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.