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1.
J Biomater Sci Polym Ed ; 35(2): 164-189, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37847579

RESUMO

Type I collagen is a predominant fibrous protein that makes up the extracellular matrix. Collagen enhances cell attachment and is commonly used in three-dimensional culture systems, to mimic the native extracellular environment, for primary sensory neurons such as dorsal root ganglia (DRG). However, the effects of collagen concentration on adult rat DRG neurite growth have not been assessed in a physiologically relevant, three-dimensional culture. This study focuses on the effects of type I collagen used in a methacrylated hyaluronic acid (MAHA)-laminin-collagen gel (triple gel) on primary adult rat DRG explants in vitro. DRGs were cultured in triple gels, and the neurite lengths and number of support cells were quantified. Increased collagen concentration significantly reduced neurite length but did not affect support cell counts. Mechanical properties, fiber diameter, diffusivity, and mesh size of the triple gels with varying collagen concentration were characterized to further understand the effects of type I collagen on hydrogel property that may affect adult rat DRG explants. Gel stiffness significantly increased as collagen concentration increased and is correlated to DRG neurite length. Collagen concentration also significantly impacted fiber diameter but there was no correlation with DRG neurite length. Increasing collagen concentration had no significant effect on mesh size and diffusivity of the hydrogel. These data suggest that increasing type I collagen minimizes adult rat DRG explant growth in vitro while raising gel stiffness. This knowledge can help develop more robust 3D culture platforms to study sensory neuron growth and design biomaterials for nerve regeneration applications.


Assuntos
Colágeno Tipo I , Hidrogéis , Ratos , Animais , Hidrogéis/farmacologia , Gânglios Espinais , Neuritos/fisiologia , Colágeno/farmacologia , Crescimento Neuronal , Células Cultivadas
2.
Forensic Sci Int Genet ; 67: 102937, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37812882

RESUMO

We have adapted an established Ampliseq microhaplotype panel for nanopore sequencing with the Oxford Nanopore Technologies (ONT) system, as a cost-effective and highly scalable solution for forensic genetics applications. For this purpose, we designed a protocol combining direct PCR amplification from unextracted DNA with ONT library construction and sequencing using the MinION device and workflow. The analysis of reference samples at input amounts of 5-10 ng of DNA demonstrates stable coverage patterns, allele balance, and strand bias, reaching profile completeness and concordance rates of ∼95%. Similar levels were achieved when using direct-PCR from blood, buccal and semen swabs. Dilution series results indicate sensitivity is maintained down to 250 pg of input DNA, and informative profiles are produced down to 62.5 pg. Finally, we demonstrated the forensic utility of the nanopore workflow by analyzing two third degree pedigrees that showed low likelihood ratio values after the analysis of an extended panel of 38 STRs, achieving likelihood ratios 2-3 orders of magnitude higher when testing with the MinION-based haplotype data.


Assuntos
Sequenciamento por Nanoporos , Humanos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , DNA/genética , DNA/análise , Reação em Cadeia da Polimerase , Técnicas de Amplificação de Ácido Nucleico , Análise de Sequência de DNA/métodos
3.
J Biomed Mater Res B Appl Biomater ; 111(11): 1903-1920, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37326300

RESUMO

Despite the significant global prevalence of chronic pain, current methods to identify pain therapeutics often fail translation to the clinic. Phenotypic screening platforms rely on modeling and assessing key pathologies relevant to chronic pain, improving predictive capability. Patients with chronic pain often present with sensitization of primary sensory neurons (that extend from dorsal root ganglia [DRG]). During neuronal sensitization, painful nociceptors display lowered stimulation thresholds. To model neuronal excitability, it is necessary to maintain three key anatomical features of DRGs to have a physiologically relevant platform: (1) isolation between DRG cell bodies and neurons, (2) 3D platform to preserve cell-cell and cell-matrix interactions, and (3) presence of native non-neuronal support cells, including Schwann cells and satellite glial cells. Currently, no culture platforms maintain the three anatomical features of DRGs. Herein, we demonstrate an engineered 3D multicompartment device that isolates DRG cell bodies and neurites and maintains native support cells. We observed neurite growth into isolated compartments from the DRG using two formulations of collagen, hyaluronic acid, and laminin-based hydrogels. Further, we characterized the rheological, gelation and diffusivity properties of the two hydrogel formulations and found the mechanical properties mimic native neuronal tissue. Importantly, we successfully limited fluidic diffusion between the DRG and neurite compartment for up to 72 h, suggesting physiological relevance. Lastly, we developed a platform with the capability of phenotypic assessment of neuronal excitability using calcium imaging. Ultimately, our culture platform can screen neuronal excitability, providing a more translational and predictive system to identify novel pain therapeutics to treat chronic pain.


Assuntos
Dor Crônica , Gânglios Espinais , Humanos , Gânglios Espinais/patologia , Gânglios Espinais/fisiologia , Dor Crônica/patologia , Neurônios , Neuritos , Hidrogéis/farmacologia
4.
Cities ; 132: 104094, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36407936

RESUMO

Positive sentiments towards urban green spaces (UGS) unequivocally increased worldwide amid COVID-19. In contrast, this paper documents that views on mobility restrictions applicable to UGS are of a contested nature. That is, while residents unambiguously report positive sentiments towards UGS, they do not share views on how to administer access to UGS-which is a matter of public policy. These contesting views reflect opposite demands that managers of UGS had to balance during the pandemic as they faced the challenge of reducing risk of spread while providing services that support physical and mental health of residents. The empirical analysis in this paper relies on views inferred through a text classification algorithm implemented on Twitter messages posted from January to October 2020, by urban residents in three Latin American countries-Argentina, Colombia, and Mexico-and Spain. The focus on Latin America is motivated by the documented lack of compliance with mobility restrictions; Spain works as a comparison point to learn differences with respect to other regions. Understanding and following in real-time the evolution of contesting views amid a pandemic is useful for managers and city planners to inform adaptation measures-e.g. communication strategies can be tailored to residents with specific views.

5.
Urban For Urban Green ; 74: 127629, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35692898

RESUMO

Urban green spaces' well documented role as a hub for physical and mental health was enhanced by restrictions to mobility issued worldwide as a response to COVID-19. In this context, managers of urban green spaces (UGS) were prompted to provide controlled access under impromptu safety protocols. This unprecedented challenge required planning and operational strengths reflecting flexibility, innovation and learning. These management features are essential for an adaptive governance - an underdeveloped research topic within the study of UGS. Using eighteen semi-structured interviews from six countries, we analyze adaptive governance as reflected by UGS managers' responses across Latin America - a region where access to UGS is a matter of public health and of environmental justice. We document responses that can be categorized based on the governance arrangement in place. On one hand, both polycentric and dedicated-management governances have been able to learn through piloting ideas, adapting personnel roles and the function of UGS infrastructure, and adjusting their decision-making process. On the other hand, managers within municipal public services areas - the most prevalent governance arrangement across Latin America - report difficulty to adapt - likely due to their dependence on political will, limited autonomy, insufficient budgets, absence of formal paths to self-funding, shortage of technical know-how, and insufficient citizens' involvement. We discuss implications of UGS adaptive governance in terms of capacity to deal with future public health, climate-related or other types of shocks.

6.
Transportation (Amst) ; : 1-65, 2022 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-35573280

RESUMO

Commuting is expensive in megacities of emerging economies. By decreasing work-related trips, teleworking may reduce congestion and commuting time. Taking Mexico City's office workers' as case study, this paper reports findings from a discrete choice experiment (DCE) exploring willingness to see a cut in monthly paycheck in exchange for teleworking two days a week from a shared office. This DCE explores preferences for bike parking spaces at shared office's facilities, and walking commuting time to shared office. This design allows estimation of willingness to pay (WTP) for teleworking across commuting time scenarios. Monthly WTP for teleworking 2 days a week starts at (2019) USD 76.68-if commuting time is zero. As 1 h of commuting time is valued at USD 61.97 on a monthly basis, WTP for teleworking 30 min away from home is USD 45.69. Wealthier respondents report higher value for commuting time and WTP for teleworking. Monthly value of bike parking infrastructure is USD 14.70-reaching USD 30.98 for commuters that walk or (motor-)bike less than 50 min. We illustrate how these stated benefits can inform cost-benefit analysis of transportation, housing, and labor policies that enable teleworking and/or reduce commuting times in Mexico City.

7.
J Orthop Res ; 38(5): 1016-1026, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31825104

RESUMO

Pain originating from an intervertebral disc (discogenic pain) is a major source of chronic low back pain. Pathological innervation of the disc by pain-sensing nerve fibers is thought to be a key component of discogenic pain, so treatment with biomaterials that have the ability to inhibit neurite growth will greatly benefit novel disc therapeutics. Currently, disc therapeutic biomaterials are rarely screened for their ability to modulate nerve growth, mainly due to a lack of models to screen neuromodulation. To address this deficit, our lab has engineered a three dimensional in vitro disc innervation model that mimics the interface between primary sensory nerves and the intervertebral disc. Further, herein we have demonstrated the utility of this model to screen the efficacy of chondroitin sulfate biomaterials to inhibit nerve fiber invasion into the model disc. Biomaterials containing chondroitin-4-sulfate (CS-A) decrease neurite growth in a uniform gel and at an interface between a growth-permissive and a growth-inhibitory gel, while chondroitin-6-sulfate (CS-C) is less neuroinhibitory. This in vitro model holds great potential for screening inhibitors of nerve fiber growth to further improve intervertebral disc replacements and therapeutics. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1016-1026, 2020.


Assuntos
Sulfatos de Condroitina/administração & dosagem , Técnicas de Cultura , Disco Intervertebral/inervação , Neuritos/efeitos dos fármacos , Animais , Materiais Biocompatíveis , Hidrogéis , Ratos
8.
Osteoporos Int ; 24(4): 1275-83, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23001114

RESUMO

UNLABELLED: This study investigated whether osteoporosis/osteopenia has an influence on the progression of periodontitis in postmenopausal women. The findings highlight that postmenopausal women with osteoporosis/osteopenia had a greater chance of presenting periodontitis than those with normal bone mineral density, particularly among nonusers of osteoporosis medications and women with a greater number of remaining teeth, showing that osteoporosis/osteopenia has had an influence on the progression of periodontitis. INTRODUCTION: This study investigated whether osteoporosis/osteopenia has an influence on the progression of periodontitis in postmenopausal women and explored the effects of use of osteoporosis medication and tooth loss on this association. METHODS: This case-control study involved 521 postmenopausal women, with minimum age of 50 years, in Feira de Santana, Bahia, Brazil. Sociodemographic characteristics, health conditions/medications, and lifestyle habits were recorded. A complete periodontal examination was performed and periodontitis was diagnosed. Bone mineral density was evaluated through lumbar spine and femoral bone densitometry, obtained using dual-energy X-ray absorptiometry. Logistic regression was used to calculate the strength of association between the occurrences of osteoporosis/osteopenia and periodontitis. RESULTS: Women with osteoporosis/osteopenia were twice as likely to present periodontitis, as were those with normal bone mineral density, even after adjusting for smoking, age, family income, and last visit to dentist (odds ratios (OR)adjusted=2.24, 95% CI [1.24-4.06], p=0.008). Among nonusers of osteoporosis medication (ORadjusted=2.51, 95% CI [1.33-4.73], p=0.004) and women with at least 10 remaining teeth (ORadjusted=2.50 95% CI [1.18-5.27], p=0.02), the odds ratio was higher and statistically significant. CONCLUSIONS: These findings highlight that postmenopausal women with osteoporosis/osteopenia had a greater chance of presenting periodontitis than those with normal bone mineral density, particularly among nonusers of osteoporosis medications and women with a greater number of remaining teeth.


Assuntos
Doenças Ósseas Metabólicas/complicações , Periodontite/etiologia , Idoso , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas Metabólicas/tratamento farmacológico , Doenças Ósseas Metabólicas/epidemiologia , Brasil/epidemiologia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Saúde Bucal/estatística & dados numéricos , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/epidemiologia , Periodontite/epidemiologia , Fatores Socioeconômicos
9.
SEMERGEN, Soc. Esp. Med. Rural Gen. (Ed. impr.) ; 32(10): 502-505, dic. 2006. tab
Artigo em Es | IBECS | ID: ibc-050871

RESUMO

El dolor es uno de los síntomas habituales por los que se consulta en Atención Primaria, que se asocia frecuentemente a procesos degenerativos de elevada prevalencia como la artrosis. Existen otras enfermedades que causan dolor esquelético como es el caso de la polimialgia reumática y que pueden confundirse con dichos procesos. Presentamos el caso de un paciente mayor diagnosticado de artrosis vertebral y osteoporosis en tratamiento que presentó además un cuadro de polimialgia reumática. Con este artículo se pretende hacer hincapié en la importancia de realizar un adecuado diagnóstico diferencial e incidir en el diagnóstico precoz de esta enfermedad, así como en el despistaje de la arteritis de células gigantes o arteritis de la temporal, enfermedad con la que se puede asociar, para su adecuado tratamiento y prevención de las complicaciones que se pueden presentar. Se comentan además aspectos referentes a la evolución, control y seguimiento de la enfermedad


Pain is an usual cause of demand for Primary Health Care often associated with high prevalence of degenerative processes such as arthrosis. There are other diseases with muscular pain like polymyalgia rheumatica that can be confused with those conditions. In the following article we are going to present the case of an elderly patient diagnosed of arthrosis of vertebral joints and osteoporosis in treatment that debuted with polymyalgia rheumatica. With this article we aim to enhance the importance of making a differential and precocious diagnosis and the early detection of giant cell arteritis or temporal arteritis, which may be associated with polymyalgia rheumatica, establishing the adequate treatment and early detection of possible complications. We comment some aspects on polymyalgia rheumatica evolution, control and follow-up


Assuntos
Masculino , Idoso , Humanos , Polimialgia Reumática/diagnóstico , Prednisona/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Diagnóstico Diferencial , Artrite Reumatoide/diagnóstico , Resultado do Tratamento
10.
J Pediatr Endocrinol Metab ; 19(11): 1327-34, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17220061

RESUMO

UNLABELLED: Data concerning the effects of GnRHa on weight gain are scarce. OBJECTIVE: To assess the variation of the body mass index (BMI) in girls during GnRHa treatment for idiopathic central precocious puberty (CPP). PATIENTS AND METHODS: Semestral anthropometric data from 176 girls treated with goserelin or leuprorelin were analyzed. RESULTS: BMI z-score increased from 1.5 +/- 0.1 SD before treatment (n = 176) to 1.7 +/- 0.2 SD after 24 months (n = 61, p = 0.008). In girls with normal weight before treatment, this variation was greater (n = 112, 0.2 +/- 0.1 SD, p = 0.01) than in those who were overweight (n = 63, -0.9 +/- 0.2 SD, p = 0.7). In the goserelin group the weight change adjusted for bone age was greater (n = 28, 0.4 +/- 0.1 SD) than in the leuprorelin group (n = 5, 0.04 +/- 0.1 SD, p = 0.05). CONCLUSIONS: A slight increase in BMI was noted, mainly in girls with normal weight before treatment. The influence of different GnRHa on weight must be further investigated.


Assuntos
Peso Corporal/fisiologia , Hormônio Liberador de Gonadotropina/análogos & derivados , Gosserrelina/uso terapêutico , Leuprolida/uso terapêutico , Puberdade Precoce/tratamento farmacológico , Estatura/efeitos dos fármacos , Estatura/fisiologia , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Criança , Pré-Escolar , Feminino , Gosserrelina/farmacologia , Humanos , Leuprolida/farmacologia , Estudos Longitudinais , Puberdade Precoce/fisiopatologia , Estudos Retrospectivos
13.
J Pediatr Endocrinol Metab ; 18(8): 807-13, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16200848

RESUMO

OBJECTIVE: To review the management of boys with short stature and delayed puberty and the testosterone priming protocol. METHODS: In 148 boys aged > 14 years seen for height < -2 SDS and constitutional delayed puberty we evaluated growth hormone (GH) secretion and final height (80 boys). RESULTS: The GH peak was < 10 microg/l after arginine-insulin tests performed with testosterone heptylate priming in 8/32 (25%) and without in 62/153 (41%), including first and second evaluations. It was low in 7/11 boys given 2 x 100 mg testosterone (14.7 +/- 1.7 microg/l) and in 1/21 given 4 x 100 mg (21.3 +/- 2.0 microg/l, p = 0.04). It was low during sleep in 4/29 (14%) boys, all having basal plasma testosterone below 3.5 nmol/l. The basal insulin-like growth factor (IGF)-I concentration was below -2 SDS in 22% of the boys evaluated. Final height was -0.8 +/- 0.1 SDS. It was similar in those with low (n = 9) and normal (n = 71) GH peak, and in those treated (n = 22) or untreated (n = 58) with testosterone. It was over 1 SDS lower than the target height in 20% and than the predicted height at the initial evaluation in 14% of the boys. Pubertal growth was not correlated with the GH peak or plasma IGF-I. CONCLUSIONS: The GH peak during the sleep is more frequently normal than the peak after stimulation. The number of testosterone doses influences the quality of priming. The medical problems involved in treating boys with delayed puberty are excluding disease and deciding on testosterone treatment.


Assuntos
Androgênios/uso terapêutico , Estatura , Hormônio do Crescimento Humano/metabolismo , Puberdade Tardia/complicações , Puberdade Tardia/terapia , Testosterona/uso terapêutico , Adolescente , Criança , Humanos , Masculino , Sono , Somatomedinas/fisiologia
14.
Arch Pediatr ; 12(11): 1661-4, 2005 Nov.
Artigo em Francês | MEDLINE | ID: mdl-16226023

RESUMO

Precocious puberty (PP) is defined in girls by the occurrence of pubertal development before the age of 8. This development raises 3 questions: 1) Is it abnormal puberty or variant of the normal? 2) If abnormal puberty, is it of central, hypothalamic-pituitary, or peripheral, ovarian or adrenal origin? 3) If central, is it idiopathic or due to a lesion, and is there indication to treat it? The PP in a girl with no previous medical history is usually of central and idiopathic origin. However, isolated central PP may reveal a CNS lesion, particularly an optic glioma with its risk of blindness. Two independent predictors of CNS lesion are the age at PP onset of less than 6 years old, and increased plasma estradiol concentration. The selection of the girls for neuroradiological imaging should be based on these two parameters. However, neuroradiological imaging remains necessary until the prospective confirmation of their predictive value.


Assuntos
Neoplasias Encefálicas/complicações , Glioma do Nervo Óptico/complicações , Puberdade Precoce/etiologia , Adolescente , Doenças das Glândulas Suprarrenais/complicações , Doenças das Glândulas Suprarrenais/diagnóstico , Idade de Início , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/patologia , Imageamento por Ressonância Magnética , Valor Preditivo dos Testes
15.
J Pediatr Endocrinol Metab ; 17(2): 149-55, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15055348

RESUMO

OBJECTIVE: To analyze the features of boys with congenital gonadotropin deficiency (CGD), and to determine the value of plasma inhibin B and anti-Müllerian hormone (AMH) for predicting testicular function and the effect of testosterone treatment. PATIENTS: We followed 19 boys for CGD, including five with Kallmann syndrome. RESULTS: The boys were seen before 14 years of age for micropenis (9 boys) or later for delayed puberty (10 boys). No testis was palpable in the scrotum in 13 patients, bilaterally in seven of them. Luteinizing hormone (LH) peak after a gonadotropin releasing hormone (GnRH) test was between 0.5 and 5.6 U/l. Plasma inhibin B was low in the four patients evaluated at less than 1 year old. AMH was low in one of them and normal in four others. Of the older patients, three lad low plasma inhibin B and four had normal concentrations; plasma AMH was low in three of them and increased in four. Testosterone treatment restored penis length to normal in all patients. CONCLUSIONS: Low plasma inhibin B and AMH concentrations may indicate testicular damage in boys with CGD.


Assuntos
Gonadotropinas/deficiência , Adolescente , Adulto , Envelhecimento/fisiologia , Hormônio Antimülleriano , Criança , Pré-Escolar , Glicoproteínas/sangue , Crescimento/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Inibinas/sangue , Masculino , Pênis/crescimento & desenvolvimento , Valor Preditivo dos Testes , Prognóstico , Puberdade/fisiologia , Hormônios Testiculares/sangue , Testículo/fisiologia , Testosterona/uso terapêutico
16.
J Pediatr Endocrinol Metab ; 15(3): 297-305, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11924932

RESUMO

Advanced puberty is defined as the onset of puberty in girls at 8-10 years of age and in boys at 9-11 years. This study analyzes adult height in 57 children with advanced puberty to evaluate the results of treating children (9 girls and 8 boys) with gonadotropin hormone releasing hormone (GnRH) analog and the impact of advanced puberty on adult height in untreated children (31 girls and 9 boys). For treated girls, adult height predicted at the onset of treatment (151.9+/-1.7 cm) was similar to the final adult height (155.3+/-1.4 cm), but lower than target height (157.2+/-1.6 cm, p = 0.04). For untreated girls, adult height predicted at the initial evaluation (156.7+/-1 cm) was also similar to adult height (157+/-1 cm), but lower than the target height (157.6+/-1 cm, p = 0.03). The adult heights of both treated and untreated girls were similar to their target heights. For treated boys, adult height predicted at the onset of treatment (173.2+/-3.1 cm) was greater than the final adult height (164.1+/-2.1 cm, p = 0.01), which was lower than target height (170.4+/-1.2 cm, p = 0.01). For untreated boys, adult height predicted at the initial evaluation (170.8+/-2.7 cm) was similar to both the adult height (169.1+/-1.9 cm) and target height (170.2+/-1.2 cm). Height gains between the onset of puberty and adult height were similar in treated (29.9+/-2.3 cm in girls and 29.8+/-1.7 cm in boys) and untreated (28.6+/-1 and 33.1+/-2 cm) children. When expressed as SD, the adult height was significantly shorter than that at 4 years in treated girls (difference 1 SD, p = 0.03), in untreated girls (difference 0.9 SD, p = 0.0002) and in treated boys (difference 0.9 SD, p = 0.02), but it was similar to that in untreated boys. Adult height was below target height by >5 cm in seven girls (two of them treated) and five boys (four of them treated). In conclusion, treating advanced puberty did not change the adult height reached by girls, and was associated with reduced growth potential in boys. The adult heights of untreated children were similar to those predicted at the initial evaluation and to target heights, but in girls they were 1 SD lower than the height at 4 years. These data suggest that advanced puberty decreases the growth potential by about 5 cm, and that GnRH analog treatment does not prevent this.


Assuntos
Estatura/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/uso terapêutico , Puberdade Precoce/tratamento farmacológico , Puberdade Precoce/fisiopatologia , Adulto , Determinação da Idade pelo Esqueleto , Criança , Feminino , Crescimento/efeitos dos fármacos , Humanos , Masculino , Estudos Retrospectivos
17.
J Clin Endocrinol Metab ; 86(11): 5245-51, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11701685

RESUMO

Cranial irradiation alters hypothalamic-pituitary function. We reevaluated 90 patients with GH deficiency caused by fractionated cranial irradiation performed at age 4.9 +/- 0.4 (SE) yr when they were 15.7 +/- 0.2 yr old. Group 1 received 18 Grays (Gy) (7 cases) or 24 Gy (21 cases) for acute lymphoblastic leukemia; group 2, 30-40 Gy for medulloblastoma (22 cases); group 3, 45-60 Gy for optic glioma and various tumors (30 cases); and group 4, 40-50 Gy for retinoblastoma (10 cases). The mean GH peaks after an arginine insulin test in group 3 (1.9 +/- 0.4 microg/liter) was lower than in groups 1 (4.8 +/- 0.5 microg/liter, P < 0.001) and 2 (3.4 +/- 0.5 microg/liter, P < 0.03). The mean plasma IGF-I concentrations in group 3 [-3.8 +/- 0.2 z score (zs)] was lower than in groups 1 (-2.4 +/- 0.3 zs, P < 0.001) and 2 (-3.1 +/- 0.2 zs, P < 0.02), as was the mean in group 4 (-3.9 +/- 0.3 zs, P < 0.01 compared with group 1 and P < 0.05 compared with group 2). GH peaks and IGF-I were correlated positively (P = 0.0001) and negatively with dose (P < 0.001 for GH and P = 0.0001 for IGF-I), but not with age at irradiation. Among the 43 patients with GH peaks below 3 microg/liter, 41 (95%) had plasma IGF-I less than -2 zs. The body mass index (BMI), plasma insulin, and leptin were similar in the four groups. They were positively correlated with each other (P < 0.001 for BMI compared with insulin and with leptin, respectively, and P < 0.01 for insulin compared with leptin), but not with age or dose of irradiation, or with markers of GH secretion. In conclusion, in patients with GH deficiency caused by cranial irradiation, the residual GH secretion and plasma IGF-I depend on the dose. Almost all the patients with severe GH deficiency had low plasma IGF-I. BMI, leptin, and insulin seem to be independent of GH status.


Assuntos
Hormônio do Crescimento Humano/deficiência , Sistema Hipotálamo-Hipofisário/efeitos da radiação , Radioterapia/efeitos adversos , Adolescente , Adulto , Biomarcadores , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Cabeça/fisiologia , Humanos , Lactente , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Leptina/metabolismo , Masculino , Neoplasias/complicações , Neoplasias/metabolismo , Neoplasias/radioterapia
18.
Clin Endocrinol (Oxf) ; 54(3): 289-94, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11298079

RESUMO

OBJECTIVE: To determine whether the initial presentation of patients with central precocious puberty (CPP) varies according to the aetiology, whether this permits the differentiation between idiopathic and organic forms, and whether the body mass index (BMI) and plasma leptin concentrations are linked to gonadotrophin secretion. DESIGN: The clinical and laboratory features of 256 patients (26 boys and 230 girls) with CPP were studied separately in boys and girls. We compared patients with idiopathic CPP (seven boys and 186 girls) to those with organic CPP, whose pubertal development revealed a central nervous system (CNS) lesion (five boys and 11 girls), and to patients with organic CPP associated with a previously treated CNS lesion (14 boys and 33 girls). RESULTS: Boys with organic CPP, having revealed or treated CNS lesions, started their puberty earlier (3.0 +/- 1.0 years and 6.7 +/- 0.5 years) than boys with idiopathic CPP (8.5 +/- 0.2 years, P < 0.01 and < 0.05). Boys with organic CPP associated with a treated CNS lesion had lower luteinizing hormone (LH)/follicle stimulating hormone (FSH) peaks ratio after stimulation with gonadotrophin releasing hormone (GnRH) (1.6 +/- 0.5) than did boys with idiopathic CPP (2.2 +/- 0.3, P < 0.05). Girls with organic CPP revealing a CNS lesion started their puberty earlier (3.6 +/- 0.9 years) than girls with idiopathic CPP (6.6 +/- 0.1 years, P < 0.0 l) and had higher LH (P < 0.01) and FSH peaks (< 0.05). Girls with organic CPP associated with a treated CNS lesion had higher BMI (1.8 +/- 0.2 z-score) than did girls with idiopathic CPP (1.3 +/- 0.1 zs, P < 0.05), higher leptin concentrations (11.7 +/- 1.8 microg/l vs. 7.7 +/- 0.5 microg/l, P < 0.0 l), LH peak (P < 0.01), FSH peak (P < 0.05) and LH/FSH peaks ratio (1 +/- 0.1 vs. 0.8 +/- 0.1, P < 0.05). Only 12.4% of the girls with idiopathic CPP had BMI-zs < 0, and their plasma leptins were positively correlated with BMI (P < 0.0001). CONCLUSIONS: The features of central precocious puberty vary according to the aetiology, but it is impossible to exclude a central nervous system lesion in a given patient with central precocious puberty without performing central nervous system imaging. This imaging remains necessary in all cases of central precocious puberty. Most of the girls with idiopathic central precocious puberty had increased BMI, but we found no correlation between plasma leptin concentrations and gonadotrophin secretion.


Assuntos
Neoplasias Hipotalâmicas/complicações , Puberdade Precoce/etiologia , Idade de Início , Índice de Massa Corporal , Criança , Pré-Escolar , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina , Humanos , Neoplasias Hipotalâmicas/sangue , Neoplasias Hipotalâmicas/diagnóstico , Leptina/sangue , Hormônio Luteinizante/sangue , Masculino , Puberdade Precoce/sangue , Fatores Sexuais , Testosterona/sangue
19.
J Pediatr (Rio J) ; 77 Suppl 2: S179-89, 2001 Nov.
Artigo em Português | MEDLINE | ID: mdl-14676881

RESUMO

OBJECTIVE: To present and discuss clinical aspects concerning the most frequent endocrine diseases in adolescents and their effects on physical and psychoaffective fields in affected patients. METHODS: Review of national and international literature combined with the authors own experience with the aim of proposing some guidelines for the management of endocrine diseases in adolescents. RESULTS: The physical and psychological impacts of these diseases on adolescents health may have different intensity. Diabetes mellitus as a chronic, self-limiting disease, with increased risk of late complications, is analyzed in more detail. Thyroid diseases and gynecomastia usually have a milder evolution, but may cause suffering and low self-esteem. CONCLUSIONS: The repercussion of these diseases, especially diabetes mellitus and gynecomastia, on the sexuality of adolescents should be taken into consideration.

20.
Eur J Pediatr ; 159(5): 348-55, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10834520

RESUMO

UNLABELLED: A suprasellar arachnoid cyst may cause disorders of growth, puberty and hypothalamic-pituitary function, due to the proximity of the cyst to the hypothalamic-pituitary area. A total of 30 patients (17 boys) with cyst diagnosed at 4.3 +/- 1 years were routinely evaluated at 5.4 +/- 1 years; 24 of them had one or multiple cyst derivations. Some 23 cases had an abnormal height, weight or puberty: short (< -2SD, 5 cases) or tall ( > 2SD, 10 cases) stature, overweight (body mass index, BMI, > 2SD, 6 cases), central precocious puberty (10 cases) and/or no progression of pubertal development (3 cases). The growth hormone (GH) peaks after pharmacological stimulation test were low (< 10 MICROg/L) in 16 patients, confirmed by a second evaluation in 8/11 of them. The plasma free thyroxine was low in five patients, prolactin was high in two and the cortisol and concomitant plasma and urinary osmolalities were normal. BMI was correlated negatively with the GH peaks (r = -0.37, P < 0.01) and positively with the plasma leptin concentrations (r = 0.55, P < 0.01). The plasma fasting insulin concentrations were also correlated negatively with the GH peaks (r = -0.55, P < 0.02) and positively with the plasma insulin-like growth factor I concentrations (r = 0.64, P < 0.002). The adult height (12 cases) was at 4SD in 1 and < -2SD in 4 patients, two of whom had precocious puberty untreated with gonadotropin releasing hormone (GnRH) analogue, and two had untreated GH deficiency. The adult height of those treated was normal. One girl had primary amenorrhoea and two boys had low plasma testosterone, despite a normal gonadotropin response to a GnRH test. CONCLUSION: Suprasellar arachnoid cysts may cause deficiencies of growth hormone and thyrotropin, stimulation of the hypothalamic-pituitary-gonadal axis, tall stature and/or overweight. These last two disorders may be due to hyperinsulinism, itself due to suprasellar arachnoid cyst.


Assuntos
Cistos Aracnóideos/complicações , Transtornos do Crescimento/etiologia , Sistema Hipotálamo-Hipofisário , Puberdade Precoce/etiologia , Adolescente , Cistos Aracnóideos/fisiopatologia , Cistos Aracnóideos/cirurgia , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Hormônio Foliculoestimulante/sangue , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/terapia , Hormônio do Crescimento/sangue , Humanos , Lactente , Fator de Crescimento Insulin-Like I/análise , Hormônio Luteinizante/sangue , Masculino , Puberdade Precoce/diagnóstico , Puberdade Precoce/terapia , Tireotropina/sangue
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