RESUMO
BACKGROUND: There are very few data on the natural history of ovarian granulosa cell tumors (OGCT) in children. The aim of this study was to determine whether early recognition and diagnosis of the initial endocrine signs could improve the outcome of these tumors. METHODS: In a nationwide study from 1990 to 2004, we analyzed the clinical, biological and pathologic data from 40 pre- and postpubertal girls presenting an OGCT. RESULTS: 1. Among the prepubertal girls (n = 29), 17 OGCTs were diagnosed on the basis of precocious pseudopuberty. None of the 17 girls had a peritoneal spread of the tumor (100% FIGO stage Ia). Diagnosis based on a tumoral or acute abdomen (12 cases) was associated with frequent intraperitoneal ruptures of the tumor (50%) and a risk of relapse (2 cases). Of the eight girls who had had a misdiagnosed precocious pseudopuberty, five had a pre- or perioperative tumoral rupture. 2. Among the postpubertal girls (n = 11), endocrine manifestations such as secondary amenorrhea or virilization had been underevaluated in three of them and the diagnosis was established from a tumoral abdomen. This clinical presentation was associated with frequent ruptures of the mass in the peritoneum (80%) and a higher risk of recurrence (30%). 3. A delayed diagnosis of OGCT despite previous endocrine signs (11 cases; 8 pre- and 3 postpubertal) was associated with a high risk of pre- or peri-operative peritoneal tumor spreading (70% FIGO stage Ic or IIc, p <0.05). The mean delay for diagnosis ranged from 3 to 11 months. CONCLUSION: This study highlights the critical role of early diagnosis of OGCT in pre- and postpubertal girls, particularly at the first seemingly banal signs of endocrine disorder. Peritoneal spread of the tumor may thereby be prevented, which improves the prognosis.
Assuntos
Tumor de Células da Granulosa/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Dor Abdominal/etiologia , Adolescente , Adulto , Amenorreia/etiologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Erros de Diagnóstico , Feminino , Tumor de Células da Granulosa/complicações , Tumor de Células da Granulosa/diagnóstico , Humanos , Lactente , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/diagnóstico , Prognóstico , Puberdade , Recidiva , Estudos Retrospectivos , Fatores de Risco , RupturaRESUMO
Multiform glioblastomas (GBM) are the most frequent and aggressive primary brain tumors in adults. The poor prognosis is due to neo-angiogenesis and cellular invasion, processes that require complex chemotaxic mechanisms involving motility, migration and adhesion. Understanding these different cellular events implies identifying receptors and transduction pathways that lead to and promote either migration or adhesion. Here we establish that glioma express the vasoactive peptide urotensin II (UII) and its receptor UT and that UT-mediated signaling cascades are involved in glioma cell migration and adhesion. Components of the urotensinergic systems, UII and UT, are widely expressed in patient-derived GBM tissue sections, glioma cell lines and fresh biopsy explants. Interestingly, gradient concentrations of UII produced chemoattracting migratory/motility effects in glioma as well as HEK293 cells expressing human UT. These effects mainly involved the G13/Rho/rho kinase pathway while partially requiring Gi/o/PI3K components. In contrast, we observed that homogeneous concentrations of UII drastically blocked cell motility and stimulated cell-matrix adhesions through a UT/Gi/o signaling cascade, partially involving phosphatidylinositol-3 kinase. Finally, we provide evidence that, in glioma cells, homogeneous concentration of UII allowed translocation of Gα13 to the UT receptor at the plasma membrane and increased actin stress fibers, lamellipodia formation and vinculin-stained focal adhesions. UII also provoked a re-localization of UT precoupled to Gαi in filipodia and initiated integrin-stained focal points. Altogether, these findings suggest that UT behaves as a chemotaxic receptor, relaying a signaling switch between directional migration and cell adhesion under gradient or homogeneous concentrations, thereby redefining sequential mechanisms affecting tumor cells during glioma invasion. Taken together, our results allow us to propose a model in order to improve the design of compounds that demonstrate signaling bias for therapies that target specifically the Gi/o signaling pathway.
Assuntos
Neoplasias Encefálicas/metabolismo , Quimiotaxia , Glioblastoma/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais , Urotensinas/metabolismo , Actinas/metabolismo , Biópsia , Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Humanos , PolimerizaçãoRESUMO
We report three boys with adrenal hypoplasia congenita (AHC) and additional findings that represent a new syndrome, IMAGe: Intrauterine growth retardation, Metaphyseal dysplasia, AHC, and Genital anomalies. Each presented shortly after birth with growth retardation and severe adrenal insufficiency. Each of the three patients had mild dysmorphic features, bilateral cryptorchidism, a small penis, and hypogonadotropic hypogonadism. Skeletal surveys revealed metaphyseal dysplasia in all three and epiphyseal dysplasia in two. The patients had documented or suspected hypercalciuria and/or hypercalcemia, resulting in nephrocalcinosis in one and in prenatal liver and spleen calcifications in another. AHC presents most often either as an isolated abnormality, caused by mutations in the DAX1 gene, or as part of an Xp21 contiguous gene syndrome, caused by a deletion of the Duchenne muscular dystrophy, glycerol kinase, and DAX1 genes. All three patients with the IMAGe association had normal creatine kinase levels and no evidence of glycerol kinase deficiency. Sequence analysis of DNA from these patients revealed no mutation in the DAX1- or steroidogenic factor-1-coding sequences, nor was a deletion of DAX1 detected. Identification of the molecular basis of the IMAGe association will give new insight into the pathogenesis of this syndromic relationship involving bone, adrenal cortical, and pituitary development.
Assuntos
Insuficiência Adrenal/congênito , Insuficiência Adrenal/complicações , Doenças do Desenvolvimento Ósseo/complicações , Retardo do Crescimento Fetal/complicações , Genitália Masculina/anormalidades , Criptorquidismo/complicações , Humanos , Hipogonadismo/complicações , Recém-Nascido , Cariotipagem , Masculino , Pênis/anormalidades , SíndromeRESUMO
Fetal male sexual differentiation is driven by two testicular hormones: testosterone (synthesized by interstitial Leydig cells) and antimüllerian hormone (AMH; produced by Sertoli cells present in the seminiferous tubules). Intersex states result either from gonadal dysgenesis, in which both Leydig and Sertoli cell populations are affected, or from impaired secretion or action of either testosterone or AMH. Until now, only Leydig cell function has been assessed in children with ambiguous genitalia, by means of testosterone assay. To determine whether serum AMH would help in the diagnosis of intersex conditions, we assayed serum AMH levels in 107 patients with ambiguous genitalia of various etiologies. In XY patients, AMH was low when the intersex condition was caused by abnormal testicular determination (including pure and partial gonadal dysgenesis) but was normal or elevated in patients with impaired testosterone secretion, whereas serum testosterone was low in both groups. AMH was also elevated during the first year of life and at puberty in intersex states caused by androgen insensitivity. In 46,XX patients with a normal male phenotype or ambiguous genitalia, in whom the diagnosis of female pseudohermaphroditism had been excluded, serum AMH levels higher than 75 pmol/L were indicative of the presence of testicular tissue and correlated with the mass of functional testicular parenchyma. In conclusion, serum AMH determination is a powerful tool to assess Sertoli cell function in children with intersex states, and it helps to distinguish between defects of male sexual differentiation caused by abnormal testicular determination and those resulting from isolated impairment of testosterone secretion or action.
Assuntos
Transtornos do Desenvolvimento Sexual/sangue , Glicoproteínas , Inibidores do Crescimento/sangue , Hormônios Testiculares/sangue , Adulto , Hormônio Antimülleriano , Criança , Pré-Escolar , Transtornos do Desenvolvimento Sexual/patologia , Transtornos do Desenvolvimento Sexual/fisiopatologia , Feminino , Humanos , Lactente , Recém-Nascido , Cariotipagem , Masculino , Puberdade , Células de Sertoli/fisiologia , Testosterona/sangueRESUMO
A double-blind clinical trial was performed on 76 patients with dentine hypersensitivity. For four weeks the patients used either a toothpaste containing nicomethanol hydrofluoride or one containing potassium nitrate and sodium monofluorophosphate. After one, two and four weeks the pain responses of the teeth to three types of stimuli were assessed. In normal conditions of oral hygiene, the nicomethanol hydrofluoride toothpaste was found at least as effective as the potassium nitrate/sodium monofluorophosphate preparation.
Assuntos
Sensibilidade da Dentina/tratamento farmacológico , Álcool Nicotinílico/uso terapêutico , Piridinas/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Álcool Nicotinílico/administração & dosagem , Cremes DentaisRESUMO
A case report of impacted maxillary third molar illustrate the limits of panoramic radiograph in topographic approach of Higmore Antrum. The CT scan in duplicate incidence appears in this case like indispensable complement to the standard X-Ray. It accurates the impacted localisation and the proceeding in the surgical treatment.
Assuntos
Dente Serotino/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Dente Impactado/diagnóstico por imagem , Adulto , Humanos , Masculino , Maxila , Radiografia PanorâmicaRESUMO
Although systematic vitamin D supplementation in adolescents remains debated, rickets is nevertheless a well recognized pathology in this age group. Adolescence is an at-risk period because of rapid growth, insufficient calcium intake and/or vitamin D status. Surveys have shown that calcium intake is insufficient (< 1000 mg a day) in 45% of boys and 71% of girls and that vitamin D status is deficient (25-OH-D < 10 ng/ml). The aims of the study carried out by the Calcium Group of the Société Française de Pédiatrie, were to evaluate the frequency of rickets, and to define the criteria for the adolescent population at risk. Forty-one adolescents with rickets were hospitalized between 1985 and 2000. Most of the cases were from the Northern France: 20 from Paris and suburbs, eight from the North-West, four from the North, four from the North-East; five were from the Center of France. The mean age was 13 years and two months for the 28 girls, and 14 years and four months for the 13 boys. Eighty per cent of the adolescents were from immigrant families (33/41): 15 were from sub-Saharan Africa, ten from North Africa, six from Pakistan and two from Turkey. Two thirds of the adolescents were hospitalized in the 2nd quarter of the year. Some adolescents suffered from lower limb pain, 16 had deformations of lower limbs, particularly genu valgum, associated with pain; seven others had either muscle spasms (4), tetany (3). Serum calcium level was low (average 1.84 mmol/l: [1.1-2.5]), and serum 25-OH D level was extremely low. Radiographic characteristics observed were metaphyseal strips on the knees, with condensed edges at times, with the presence of bone demineralization. The treatment combined calcium and vitamin D, and was often administered intravenously when a hypocalcemia was detected. Rickets is not frequent in adolescents, but nonetheless this pathology is not exceptional, and the number of cases is probably under-estimated. Rickets affects immigrant adolescents in particular but nevertheless could also present a certain risk period for the general population.
Assuntos
Emigração e Imigração , Raquitismo/etiologia , Vitamina D/uso terapêutico , Adolescente , Cálcio/administração & dosagem , Estudos Epidemiológicos , Etnicidade , Feminino , França/epidemiologia , Humanos , Incidência , Masculino , Raquitismo/epidemiologia , Fatores de RiscoRESUMO
In order to evaluate the predictive value of parasitaemia, this parameter was measured on admission in 69 Gabonese children aged from 3 to 13 years hospitalized for Plasmodium falciparum malarial attacks. Fourteen of these children had cerebral malaria, 5 had isolated convulsions and 50 had uncomplicated attacks. The parasitaemia values measured were compared with those found in asymptomatic children of the same age range carrying trophozoites. There were no significant differences in mean parasitaemia count between the 3 types of malarial attack, and only the asymptomatic carriers had significantly lower counts. However, the wide scattering of individual values within each group indicated that simple measurement of parasitaemia is not discriminative enough to predict the course of malarial attacks in children living in endemic regions. In particular, malarial attacks with very low or very high parasitaemia value are possible, but similar values are found in asymptomatic carriers.
Assuntos
Malária Falciparum/sangue , Adolescente , Antimaláricos/uso terapêutico , Portador Sadio , Criança , Pré-Escolar , Gabão , Humanos , Malária Falciparum/complicações , Malária Falciparum/tratamento farmacológico , Fenantrenos/uso terapêutico , Quinina/uso terapêutico , Convulsões Febris/etiologiaRESUMO
In patients, cancer and treatments provoke cognitive impairments referred to "chemofog". Here a validated neurobehavioral animal model, the unique way to explore causal direct links between chemotherapy used in clinical practices and brain disorders, allowed investigation of the direct long-term impact of colo-rectal cancer chemotherapy on cognition and cerebral plasticity. Young and aged mice received three injections every 7 days during 2 weeks of 5-fluorouracil either alone (5-FU, 37.5 mg/kg) or in combination with oxaliplatin (3 mg/kg) or with glucose (5%). The long-term effects (from day 24 to day 60) of chemotherapy were tested on emotional reactivity, learning and memory, behavioral flexibility and hippocampal cell plasticity. 5-FU (in saline)-treated aged and also young mice exhibited specific altered cognitive flexibility and behavioral hyper-reactivity to novelty, whereas the combination 5-FU (in saline)/oxaliplatin (in glucose) did not provoke any cognitive dysfunction. We thus observed that glucose counteracted 5-FU-induced altered executive functions and hippocampal cell proliferation in vivo, and protected neural stem cells in vitro from toxicity of 5-FU or oxaliplatin. In conclusion, these data suggest that the lasting chemotherapy-induced selective impairment of executive functions, whatever the age, and associated with a reduced number of hippocampal proliferating cells, can be counteracted by co-administration with glucose.
Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Antineoplásicos/efeitos adversos , Fluoruracila/efeitos adversos , Glucose/uso terapêutico , Nootrópicos/uso terapêutico , Compostos Organoplatínicos/efeitos adversos , Fatores Etários , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quimioterapia Adjuvante , Cognição/efeitos dos fármacos , Cognição/fisiologia , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Função Executiva/efeitos dos fármacos , Função Executiva/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/fisiologia , Testes Neuropsicológicos , Oxaliplatina , Fatores de TempoRESUMO
The Floating Harbor syndrome is a rare genetic disease characterized by a triad of clinical signs: specific dysmorphic facial features, short stature with delayed bone age, and language and speech disorders. These signs are, in most cases, associated with borderline normal intelligence to moderate delay concerning intellectual functioning. We report an extensive neuropsychological evaluation for an adult female patient and show, in particular, a severe visuospatial impairment. We discuss this deficit in the light of the previous reported cases and suggest that visuospatial abilities should be explored more systematically.
Assuntos
Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Anormalidades Craniofaciais/complicações , Transtornos do Crescimento/complicações , Comunicação Interventricular/complicações , Testes Neuropsicológicos , Anormalidades Múltiplas/psicologia , Adulto , Atenção/fisiologia , Anormalidades Craniofaciais/psicologia , Função Executiva/fisiologia , Feminino , Transtornos do Crescimento/psicologia , Comunicação Interventricular/psicologia , Humanos , Inteligência , Transtornos da Linguagem/diagnóstico , Transtornos da Linguagem/etiologia , Memória/fisiologia , Transtornos do Humor/etiologia , Personalidade , Percepção Espacial/fisiologiaRESUMO
CONTEXT: Steroid 21-hydroxylase deficiency is the most common enzymatic defect causing congenital adrenal hyperplasia with genotype/phenotype relationships for common mutations. Novel mutations of the CYP21A2 gene must be well studied to propose right genetic counseling for patients. OBJECTIVE: Thirteen CYP21 mutations have been studied. A detailed description of phenotype was performed for all mutations (p.I77T, p.L167P, p.I230T, p.R233K, p.G291S, p.G292D, p.E320K, p.R341P, p.R354H, p.R369W, p.R408C, p.G424S, and p.R426H). In vitro and in silico studies were performed only for those not previously described (p.L167P, p.I230T, p.R233K, p.G292D, p.E320K, and p.R369W). RESULTS: Regarding phenotype, patients with 10 of these mutations had a classical form. A patient with isolated p.I230T presented with nonclassical form and a patient with the association p.I230T + p.V281L in cis presented with a more severe phenotype. The p.R233K mutation was detected in a carrier partner. A patient with p.R369W presented with an intermediate form. Functional studies showed that all mutations except p.I230T and p.R369W decreased enzyme activity more than p.P30L: severity of p.R369W was intermediate between p.P30L and p.V281L, and finally p.I230T was less severe than p.V281L. Mutation analysis in a three-dimensional model structure of the CYP21 protein explained the observed in vitro effects, severe mutations being implicated in important functional domains of the protein. CONCLUSION: According to phenotype and functional studies, 11 of the mutations described, except the isolated p.R369W and p.I230T, may be responsible for a severe phenotype underlying the necessity to manage children having them. The p.I230T is a nonclassical mutation, and for the p.R369W, we need more cases to precise its severity.
Assuntos
Hiperplasia Suprarrenal Congênita/enzimologia , Hiperplasia Suprarrenal Congênita/genética , Mutação/genética , Esteroide 21-Hidroxilase/genética , 17-alfa-Hidroxiprogesterona/metabolismo , Animais , Western Blotting , Células COS , Células Cultivadas , Chlorocebus aethiops , Estudos de Associação Genética , Predisposição Genética para Doença/genética , Humanos , Fenótipo , Conformação Proteica , Esteroide 21-Hidroxilase/metabolismo , Fatores de TempoAssuntos
Estatura , Psicologia do Adolescente , Adulto , Idoso , Feminino , Humanos , Estado Civil , Pessoa de Meia-Idade , Ocupações , Autoimagem , Inquéritos e QuestionáriosAssuntos
Trombose das Artérias Carótidas/complicações , Doenças Linfáticas/complicações , Síndrome de Linfonodos Mucocutâneos/complicações , Artéria Carótida Interna , Pré-Escolar , Erros de Diagnóstico , Feminino , Humanos , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/patologia , Poliarterite Nodosa/diagnósticoRESUMO
OBJECTIVE: To analyze the clinical and histological findings in boys with bilateral anorchia and the response to testosterone treatment on penis length. STUDY DESIGN: Patients were divided into two groups according to the absence (group A, n = 29) or the presence (group B, n = 26) of palpable intrascrotal or inguinal mass at first clinical examination. RESULTS: A micropenis was found in 46% of patients (n = 24) with a similar proportion in both groups. Testosterone treatment induced a mean penis length gain of 1.9 +/- 1.3 SDS (standard deviation score). However, micropenis persisted in six patients. Histological examination (n = 18) confirmed the absence of any testicular structure with deferent ducts being present unilaterally or bilaterally in all but three patients. In these three patients, a hemorrhagic testis, probably as a result of a mechanical torsion, was found. CONCLUSIONS: The presence of isolated micropenis in almost half of patients with bilateral anorchia strongly suggests that the testicular damage frequently occurs during the second half of gestation after male sexual differentiation. In most cases, testosterone treatment stimulates the penile growth. Although the pathogenesis of bilateral anorchia may be heterogeneous, our study suggests that gonads may have been functionally abnormal before they disappeared, and suggests that some patients have an intrinsic endocrine disorder.
Assuntos
Androgênios/uso terapêutico , Eunuquismo/tratamento farmacológico , Eunuquismo/patologia , Doenças do Pênis/tratamento farmacológico , Doenças do Pênis/patologia , Testosterona/uso terapêutico , Androgênios/deficiência , Criança , Pré-Escolar , Eunuquismo/congênito , Eunuquismo/cirurgia , França/epidemiologia , Genitália Masculina/anormalidades , Genitália Masculina/efeitos dos fármacos , Genitália Masculina/crescimento & desenvolvimento , Genitália Masculina/cirurgia , Humanos , Lactente , Recém-Nascido , Masculino , Doenças do Pênis/congênito , Doenças do Pênis/cirurgia , Torção do Cordão Espermático/congênito , Torção do Cordão Espermático/patologia , Torção do Cordão Espermático/cirurgia , Testosterona/deficiência , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos MasculinosRESUMO
Cutaneous and mucous lesions are uncommon and very often confusing in Horton's disease. In this case report, adding to this confusing aspect, the patient's medical history and clinical signs led the investigations in a totally different direction. Facing this isolated lesion of the tongue and the negative biopsy of the temporal superficial artery, the diagnosis of Horton's disease was finally confirmed by the good reaction following corticoid therapy.
Assuntos
Poliarterite Nodosa/diagnóstico , Prednisolona/análogos & derivados , Doenças da Língua/diagnóstico , Idoso , Diagnóstico Diferencial , Feminino , Arterite de Células Gigantes/diagnóstico , Humanos , Poliarterite Nodosa/tratamento farmacológico , Prednisolona/uso terapêutico , Língua/irrigação sanguínea , Doenças da Língua/tratamento farmacológicoRESUMO
Results of an inquiry in adults patients (18-53 years of age) coming from three centers (1 in Rouen & 2 in Paris), 213 questionnaires were sent. 105 answers were received. Scholar achievement: only secondary cycle in 6%, Secondary cycle + professional course in 22% and tertiary cycle in 44%. No scholar ship in 2%, 26% were still ongoing studies. Professions: 18% are unemployed (24%), Secretary jobs: 10%, Health professions (altogether): 18%, Teachers: 8%, Clerks: 7%, Executive jobs: 8% and Miscellaneous jobs: 5%. 3% have an handicapped status. The small height was a career obstacle in 29%. Affective life. Age of first sexual intercourse was 19-22 years. 17 are or were married and 15% are living in couple. But 58% have not any sexual life whatsoever. These women are divided on the ways to cure the sterility. Few among the oldest have attempted adoption or medically assisted procreation, with each time low rate of success. 26% have psychological disturbances which were serious in 6% mainly due to depression.
Assuntos
Desenvolvimento Psicossexual , Qualidade de Vida , Síndrome de Turner/psicologia , Adolescente , Adulto , Afeto , Escolaridade , Feminino , França , Humanos , Estado Civil , Pessoa de Meia-Idade , Ocupações , Inquéritos e QuestionáriosRESUMO
In three young girls with isosexual precocity and fibrous dysplasia of bones, plasma gonadotropins (LH and FSH) response to releasing hormone (LH-RH) has been much under the mean response in true female precocious puberty. These data and those previously reported in the literature suggest that MacCune-Albright's syndrome correlates to an hypothalamo-pituitary dysfunction rather than to a true prematurity.
Assuntos
Displasia Fibrosa Óssea/complicações , Gonadotropinas Hipofisárias/metabolismo , Puberdade Precoce/complicações , 17-Hidroxicorticosteroides/urina , 17-Cetosteroides/urina , Determinação da Idade pelo Esqueleto , Criança , Pré-Escolar , Doenças do Sistema Endócrino/complicações , Doenças do Sistema Endócrino/tratamento farmacológico , Estradiol/sangue , Estrona/sangue , Feminino , Displasia Fibrosa Óssea/tratamento farmacológico , Hormônio Liberador de Gonadotropina/análise , Gonadotropinas Hipofisárias/urina , Hormônio do Crescimento/uso terapêutico , Humanos , Lactente , Medroxiprogesterona/uso terapêutico , Transtornos da Pigmentação/complicações , Transtornos da Pigmentação/tratamento farmacológico , Puberdade Precoce/tratamento farmacológico , Síndrome , Tiroxina/uso terapêuticoRESUMO
A child is described who developed acute ischaemic necrosis of the oesophagus complicating an otherwise typical case of anaphylactoid purpura. This episode was preceded by a necrotising ileitis requiring intestinal resection and ileostomy. The histological similarities of the lesions in the oesophagus and the ileum suggest a common cause connected with the anaphylactoid purpura.