RESUMEN
Organization of health care of a patient followed in pediatric oncology is not limited to cancer treatment. It includes a whole range of supportive care. Some are common to the supportive care offered in adult oncology, such as pain management and nutritional support. However, there are pediatric specificities. Others are more peculiar to children, such as education and information for young patients, and require a specific framework and innovative tools. The young age of patients and the improvement in survival rates in pediatric oncology also lead to questioning the temporality of supportive care by considering access to supportive care beyond the active phase of the disease. This review explains some of these different specificities: information and communication to the patient and his parents, assessment and management of pain, nutritional support but also schooling, long-term follow-up and screening sequelae induced by the disease and its treatments.
Asunto(s)
Oncología Médica , Neoplasias , Adulto , Niño , Comunicación , Humanos , Neoplasias/complicaciones , Neoplasias/diagnóstico , Neoplasias/terapia , Manejo del Dolor , PadresRESUMEN
Prevalence of pituitary incidentaloma is variable: between 1.4% and 27% at autopsy, and between 3.7% and 37% on imaging. Pituitary microincidentalomas (serendipitously discovered adenoma <1cm in diameter) may increase in size, but only 5% exceed 10mm. Pituitary macroincidentalomas (serendipitously discovered adenoma>1cm in diameter) show increased size in 20-24% and 34-40% of cases at respectively 4 and 8years' follow-up. Radiologic differential diagnosis requires MRI centered on the pituitary gland. Initial assessment of nonfunctioning (NF) microincidentaloma is firstly clinical, the endocrinologist looking for signs of hypersecretion (signs of hyperprolactinemia, acromegaly or Cushing's syndrome), followed up by systematic prolactin and IGF-1 assay. Initial assessment of NF macroincidentaloma is clinical, the endocrinologist looking for signs of hormonal hypersecretion or hypopituitarism, followed up by hormonal assay to screen for hypersecretion or hormonal deficiency and by ophthalmologic assessment (visual acuity and visual field) if and only if the lesion is near the optic chiasm (OC). NF microincidentaloma of less than 5mm requires no surveillance; those of≥5mm are not operated on but rather monitored on MRI at 6months and then 2years. Macroincidentaloma remote from the OC is monitored on MRI at 1year, with hormonal exploration (for anterior pituitary deficiency), then every 2years. When macroincidentaloma located near the OC is managed by surveillance rather than surgery, MRI is recommended at 6months, with hormonal and visual exploration, then annual MRI and hormonal and visual assessment every 6months. Surgery is indicated in the following cases: evolutive NF microincidentaloma, NF macroincidentaloma associated with hypopituitarism or showing progression, incidentaloma compressing the OC, possible malignancy, non-compliant patient, pregnancy desired in the short-term, or context at risk of apoplexy.
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Neoplasias Hipofisarias/terapia , Consenso , Humanos , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/epidemiología , PrevalenciaRESUMEN
Clinically NFPA is currently the preferred term for designing all the pituitary adenomas which are not hormonally active (in other words, not associated with clinical syndromes such as amenorrhea-galactorrhea in the context of prolactinomas, acromegaly, Cushing's disease or hyperthyroidism secondary to TSH-secreting adenomas). They account for 15-30% of pituitary adenomas. Diagnosis is usually made either in the context of mass effect due to a macroadenoma or, increasingly, fortuitously during imaging performed for some unrelated purpose; the latter case is known as pituitary incidentaloma. Surgery is indisputably indicated in case of tumoral syndrome, but other aspects of NFPA (hormonal work-up, follow-up, and especially postoperative follow-up, management of remnant or recurrence, the special case of incidentaloma, or apoplexy) remain controversial. The French Endocrinology Society (SFE) therefore set up an expert working group of endocrinologists, neurosurgeons, ophthalmologists, neuroradiologists, pathologists and biologists to draw up guidelines, at the 2012 SFE Congress in Toulouse, France. The present article presents the guidelines suggested by this group of French-speaking experts.
Asunto(s)
Adenoma/terapia , Neoplasias Hipofisarias/terapia , Adenoma/fisiopatología , Adenoma/cirugía , Consenso , Humanos , Apoplejia Hipofisaria/fisiopatología , Apoplejia Hipofisaria/cirugía , Apoplejia Hipofisaria/terapia , Neoplasias Hipofisarias/fisiopatología , Neoplasias Hipofisarias/cirugíaRESUMEN
CONTEXT: Outcomes of congenital adrenal hyperplasia due to classic 21-hydroxylase deficiency (21OHD) have been widely studied in children and women, but less so in men. OBJECTIVE: The objective was to analyze data from a network of metropolitan French teaching hospitals on the clinical outcome of classic 21OHD in a large sample of congenital adrenal hyperplasia/21OHD-genotyped adult men, and particularly the impact of 21OHD on the gonadotrope axis, testicular function, and fertility. METHODS: From April 2011 to June 2014, tertiary endocrinology departments provided data for 219 men with 21OHD (ages, 18-70 y; 73.6% salt wasters, 26.4% simple virilizers). Testicular sonography was performed in 164 men, and sperm analysis was performed in 71 men. RESULTS: Mean final height was 7.8 cm lower than in a reference population. Obesity was more common, and mean blood pressure was lower than in the reference population. None of the patients were diabetic, and lipid status was generally normal. Blood electrolyte status was normal in the vast majority of men, despite markedly elevated ACTH and renin levels. Serum progesterone, 17-hydroxyprogesterone, and androstenedione levels were above normal in the vast majority of cases. Hormonal profiling variously showed a normal gonadotrope-testicular axis, gonadotropin deficiency, or primary testicular insufficiency. Testicular sonography revealed testicular adrenal rest tumors (TARTs) in 34% of 164 men. Serum inhibin B and FSH levels were significantly lower and higher, respectively, in patients with TARTs. Severe oligospermia or azoospermia was found in 42% of patients and was significantly more prevalent in men with TARTs (70%) than in men with normal testes (3.6%; P < .0001). Among men living with female partners, TARTs were significantly more prevalent in those who had not fathered children. CONCLUSION: We report the spectrum of testicular/gonadotrope axis impairment in the largest cohort of 21OHD men studied to date. Our results suggest that French men with 21OHD managed in specialized centers frequently have impaired exocrine testicular function but that its reproductive implications are often overlooked.
Asunto(s)
Hiperplasia Suprarrenal Congénita , Hormonas Esteroides Gonadales/sangre , Gonadotrofos/fisiología , Sistema Hipotálamo-Hipofisario/fisiología , Testículo/fisiología , Adolescente , Hiperplasia Suprarrenal Congénita/sangre , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/epidemiología , Hiperplasia Suprarrenal Congénita/fisiopatología , Tumor de Resto Suprarrenal/diagnóstico por imagen , Tumor de Resto Suprarrenal/epidemiología , Adulto , Anciano , Recolección de Datos , Francia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Semen , Neoplasias Testiculares/diagnóstico por imagen , Neoplasias Testiculares/epidemiología , Testículo/diagnóstico por imagen , Ultrasonografía , Adulto JovenRESUMEN
When a nursing procedure needs to be carried out, the child and his or her parents can adopt a comfortable position and participate as best as they can during the procedure. Explanation sheets and personal advice enable such procedures to be carried out in the best conditions for the families and caregivers.
Asunto(s)
Servicios de Salud del Niño , Relaciones Padres-Hijo , Participación del Paciente , Relaciones Profesional-Familia , Niño , HumanosRESUMEN
Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.
Asunto(s)
Hipófisis/patología , Neoplasias Hipofisarias/clasificación , Neoplasias Hipofisarias/patología , Adolescente , Adulto , Factores de Edad , Anciano , Estudios de Casos y Controles , Supervivencia sin Enfermedad , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Hipófisis/ultraestructura , Neoplasias Hipofisarias/cirugía , Pronóstico , Recurrencia , Estudios Retrospectivos , Sensibilidad y Especificidad , Factores Sexuales , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the degree of E2 deficiency in male congenital hypogonadotropic hypogonadism (CHH), and its response to different hormonal treatments. DESIGN: Retrospective and prospective studies. SETTING: Academic institution. PATIENT(S): Untreated or treated CHH, healthy men, untreated men with Klinefelter syndrome (KS). INTERVENTION(S): Serum sex hormone-binding globulin (SHBG) and total E2 (TE2) as well as bioavailable (BE2) and free (FE2) levels were measured and determined. MAIN OUTCOME MEASURE(S): Total, bioavailable, and free testosterone, TE2, BE2, FE2 were compared in normal men, untreated and treated CHH and in untreated KS. RESULT(S): TE2, BE2, and FE2 levels were very significantly lower in untreated patients with CHH (n=91) than in controls (n=63) and in patients with KS (n=45). The TE2 correlated positively with serum total T in patients with CHH. The TE2 also correlated very positively with serum LH in the combined population of patients with CHH and healthy men, suggesting that low E2 levels in CHH are due to severe LH-driven T deficiency. All fractions of circulating E2 were very significantly higher in patients with CHH receiving T enanthate (n=101) or the FSH-hCG combination (n=88) than in untreated patients with CHH. Contrary to dihydrotestosterone (DHT), both T enanthate and combined FSH-hCG therapy significantly and prospectively increased TE2 levels in patients with CHH. CONCLUSION(S): Contrary to KS, the male hypogonadism observed in CHH is associated with profound E2 deficiency, which can be overcome by aromatizable androgen or combined gonadotropin therapy.
Asunto(s)
Andrógenos/administración & dosificación , Gonadotropina Coriónica/administración & dosificación , Dihidrotestosterona/administración & dosificación , Estradiol/deficiencia , Hormona Folículo Estimulante/administración & dosificación , Terapia de Reemplazo de Hormonas , Hipogonadismo/tratamiento farmacológico , Testosterona/análogos & derivados , Adolescente , Adulto , Análisis de Varianza , Biomarcadores/sangre , Estradiol/sangre , Humanos , Hipogonadismo/sangre , Hipogonadismo/congénito , Síndrome de Klinefelter/sangre , Síndrome de Klinefelter/tratamiento farmacológico , Hormona Luteinizante/sangre , Masculino , Persona de Mediana Edad , Paris , Estudios Prospectivos , Estudios Retrospectivos , Globulina de Unión a Hormona Sexual/análisis , Testosterona/administración & dosificación , Testosterona/sangre , Testosterona/deficiencia , Resultado del Tratamiento , Adulto JovenRESUMEN
CONTEXT: Adequate postoperative management of nonfunctioning pituitary macroadenomas (NFMAs) remains a challenge for the clinician. OBJECTIVE: To identify predictive factors of NFMA relapse after initial surgery. PATIENTS AND METHODS: This retrospective study included 142 patients operated for an NFMA in two academic centers (CHU Bicêtre in France and UCL St Luc in Belgium). The rate of tumor relapse, defined as recurrence after total surgical resection or regrowth of a surgical remnant, as well as predictive factors was analyzed. RESULTS: During a mean follow-up of 6.9 years, 10 out of 42 patients (24%) who had complete macroscopic resection of their tumor had recurrence, and 47 out of 100 patients (47%) with a surgical remnant experienced regrowth. The overall relapse rates were 25, 43, and 61% at 5, 10, and 15 years respectively. Invasion of the cavernous sinus, absence of immediate radiotherapy after the first neurosurgery, and immunohistochemical features of the tumor (mainly positive immunostaining for several hormones or for hormones other than gonadotropins) were independent risk factors for tumor relapse. Incomplete excision was only associated with relapse when invasion was withdrawn from the analysis, suggesting that these two factors are closely linked. CONCLUSION: NFMAs frequently recur/regrow after initial surgery, particularly when tumor is invasive, precluding complete removal. Immunohistochemical features such as positive immunostaining for several hormones or for hormones other than gonadotropins could help to predict undesirable outcomes.
Asunto(s)
Adenoma/patología , Recurrencia Local de Neoplasia/patología , Neoplasias Hipofisarias/patología , Adenoma/cirugía , Adulto , Anciano , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Hipófisis/patología , Hipófisis/cirugía , Neoplasias Hipofisarias/cirugía , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Estadísticas no ParamétricasRESUMEN
Non-functioning pituitary adenomas (NFPAs) may be locally invasive. Markers of invasiveness are needed to guide patient management and particularly the use of adjuvant radiotherapy. To examine whether invasive NFPAs display a specific gene expression profile relative to non-invasive tumors, we selected 40 NFPAs (38 of the gonadotroph type) and classified them as invasive (n=22) or non-invasive (n=18) on the basis of magnetic resonance imaging and surgical findings. We then performed pangenomic analysis with the 44k Agilent human whole genome expression oligonucleotide microarray in order to identify genes with differential expression between invasive and non-invasive NFPAs. Candidate genes were then tested in qRT-PCR. Prediction class analysis showed that the expression of 346 genes differed between invasive and non-invasive NFPAs (P<0.001), of which 233 genes were up-regulated and 113 genes were down-regulated in invasive tumors. On the basis of Ingenuity networks and the degree of up- or down-regulation in invasive versus non-invasive tumors, 35 genes were selected for expression quantification by qRT-PCR. Overexpression of only four genes was confirmed, namely IGFBP5 (P=0.02), MYO5A (P=0.04), FLT3 (P=0.01), and NFE2L1 (P=0.02). At the protein level, only myosin 5A (MYO5A) immunostaining was stronger in invasive than in non-invasive NFPAs. Molecular signature allows to differentiate 'grossly' invasive from non-invasive NFPAs. The product of one of these genes, MYO5A, may be a useful marker of tumor invasiveness.
Asunto(s)
Adenoma/genética , Recurrencia Local de Neoplasia/genética , Neoplasias Hipofisarias/genética , Adenoma/metabolismo , Adenoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Masculino , Análisis por Micromatrices , Persona de Mediana Edad , Cadenas Pesadas de Miosina/genética , Cadenas Pesadas de Miosina/metabolismo , Miosina Tipo V/genética , Miosina Tipo V/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/patología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaAsunto(s)
Niño Hospitalizado/psicología , Competencia Clínica , Comunicación , Instrucción por Computador/métodos , Educación Continua en Enfermería/métodos , Enfermería Pediátrica/educación , CD-ROM , Niño , Organizaciones del Consumidor , Francia , Humanos , Enfermeras Administradoras , Relaciones Enfermero-Paciente , Personal de Enfermería en Hospital/educación , Personal de Enfermería en Hospital/psicología , Enfermería Pediátrica/métodosRESUMEN
CONTEXT: A discrepancy between serum GH and IGF1 concentrations is frequent in patients with acromegaly. Here, we examined whether the exon 3-deleted (d3) GH receptor (GHR) variant, which has been linked to increased responsiveness to GH treatment in short children, influences the GH/IGF1 relationship in patients with acromegaly. OBJECTIVE: To study the possible influence of the GHR genotype on the GH/IGF1 relationship in untreated acromegalic patients. DESIGN: GHR genotype analysis with retrospective clinical and biochemical data collection performed in a single third-reference medical center. PATIENTS AND METHODS: Clinical data were obtained from the medical records of 105 acromegalic patients who had GH and IGF1 assays in the same laboratory and who were genotyped for the full-length (fl) or d3-GHR alleles. RESULTS: The distribution of GHR genotypes was 51% fl/fl, 30% fl/d3, and 19% d3/d3. Patients with d3/d3 genotype were younger than the patients in the other two groups (P<0.05). Baseline GH and IGF1 concentrations did not differ among the three groups. The linear correlation between GH and IGF1 concentrations was similar in the three genotypic groups. CONCLUSIONS: The exon 3 GHR genotype does not affect the GH/IGF1 relationship in untreated acromegalic patients with high circulating GH and IGF1 levels.
Asunto(s)
Acromegalia/sangre , Acromegalia/genética , Proteínas Portadoras/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Adulto , Anciano , ADN/química , ADN/genética , Femenino , Genotipo , Hormona de Crecimiento Humana/sangre , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Estudios Retrospectivos , Adulto JovenRESUMEN
Pituitary adenomas are benign tumors that can be classified according to the type of hormone they produce, immunocytochemical characteristics (which generally confirm the clinical classification) or, as proposed by WHO in 2004, specific differentiation markers of the various ligneages. The pathophysiology of pituitary adenomas is largely unknown. Although a clonal origin is very likely, no univocal molecular abnormality (except for gsp mutations, found in 40% of somatotropic adenomas) has yet been found. Studies of cell cycle proteins, growth factors and oncogenes are beginning to shed light on the complex underlying mechanisms.
Asunto(s)
Adenoma/clasificación , Neoplasias Hipofisarias/clasificación , Neoplasias Hipofisarias/fisiopatología , Adenoma/genética , Adenoma/metabolismo , Adenoma/patología , Adenoma/fisiopatología , Animales , Proteínas de Ciclo Celular/fisiología , Transformación Celular Neoplásica/genética , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular/fisiología , Masculino , Ratones , PPAR gamma/efectos de los fármacos , PPAR gamma/fisiología , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/patología , Proteómica , Receptores de Estrógenos/fisiología , Receptores de Factores de Crecimiento/fisiología , Organización Mundial de la SaludRESUMEN
It has been shown that the hepatitis C virus (HCV) core protein reduces the activity of the microsomal triglyceride transfer protein (MTP) and could lead to steatosis in HCV-infected patients. Experimentally, apolipoprotein-AII (apoAII), which restores triglyceride secretion altered by the HCV core protein, could be protective against HCV steatosis. On the other hand, increasing plasma concentrations of mouse apoAII in transgenic mice produced several aspects of insulin-resistance syndrome, which also is implicated in the pathogenesis of HCV steatosis. This study was designed to investigate the role of apoAII in HCV-related steatosis in humans. Sixty-five hospitalized patients with chronic HCV were included in this study to assess the effects of apoAII, body mass index (BMI), age, insulin sensibility (HOMA), and leptin level on steatosis. Steatosis was observed in 55.3% of patients. Apo-AII was significantly associated with HOMA and with leptin concentrations. In univariate analyses, age, BMI, increased leptin level, increased HOMA, and increased apoAII concentration were associated with steatosis. In multivariate analysis, steatosis was associated with apoAII concentration, age, gender, and BMI. Contrary to previous hypotheses, apoAII is not a protective factor against HCV steatosis but is significantly associated with the development of liver steatosis. The fact that the plasma levels of apoAII correlate with HOMA and leptin levels in HCV-infected patients suggests that apoAII may contribute to hepatic steatosis progression in relationship to visceral obesity, insulin resistance, and metabolism of triglyceride-rich lipoproteins.
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Apolipoproteína A-II/sangre , Hígado Graso/sangre , Hepatitis C Crónica/complicaciones , Adulto , Biomarcadores/sangre , Biopsia , Índice de Masa Corporal , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Hígado Graso/etiología , Hígado Graso/patología , Femenino , Estudios de Seguimiento , Hepatitis C Crónica/sangre , Hepatitis C Crónica/patología , Humanos , Masculino , Persona de Mediana Edad , Nefelometría y Turbidimetría , PronósticoRESUMEN
BACKGROUND: Acromegaly, which may be present in patients with McCune-Albright syndrome (MCAS), in association with café-au-lait spots, precocious puberty, and fibrous dysplasia, is often difficult to treat surgically because skull base bone dysplasia prevents the removal of the pituitary adenoma. Somatostatin analogs (SAs) generally give only partial responses. The use of radiotherapy (RT) is controversial because of a possible risk of bone sarcomatous transformation. AIM: This study was a retrospective analysis of the efficacy and adverse effects of different treatment modalities in six patients with both MCAS and acromegaly. PATIENTS AND METHODS: Because surgery was impossible and SA failed to normalize GH/IGF-I hypersecretion, five of the six patients received fractionated RT (45-55 Grays). Three patients (two with previous RT) were also prescribed pegvisomant. We analyzed the clinical features of acromegaly, GH, and IGF-I concentrations and bone radiological features. RESULTS: GH and IGF-I concentrations fell after RT (median follow-up, 5 yr; range, 0.5-9 yr). Symptoms of acromegaly improved in parallel. Bone sarcomatous transformation was only noted in one patient in a region (the mandible) outside the radiation field. RT alone and/or combined with SA failed to normalize GH/IGF-I levels in the five patients concerned. In contrast, IGF-I levels normalized very rapidly (5-9 months) in the three patients receiving pegvisomant (10-20 mg/d). CONCLUSION: RT may be an option for the treatment of acromegaly in patients with MCAS when surgery is impossible and SA therapy is ineffective. However, although no bone sarcomatous transformation was observed within the radiation field in this series, this risk cannot be ruled out. As shown in this small series of severely affected patients, pegvisomant therapy may thus be useful to normalize IGF-I levels rapidly.
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Acromegalia/complicaciones , Acromegalia/tratamiento farmacológico , Acromegalia/radioterapia , Displasia Fibrosa Poliostótica/complicaciones , Displasia Fibrosa Poliostótica/tratamiento farmacológico , Displasia Fibrosa Poliostótica/radioterapia , Hormona de Crecimiento Humana/análogos & derivados , Adulto , Terapia Combinada , Resistencia a Medicamentos/efectos de los fármacos , Resistencia a Medicamentos/efectos de la radiación , Huesos Faciales/diagnóstico por imagen , Femenino , Hormona de Crecimiento Humana/sangre , Hormona de Crecimiento Humana/metabolismo , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Hipotálamo/efectos de la radiación , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Persona de Mediana Edad , Hipófisis/efectos de la radiación , Radiografía , Estudios Retrospectivos , Cráneo/diagnóstico por imagen , Somatostatina/análogos & derivadosRESUMEN
BACKGROUND: The pituitary tumour transforming gene (pttg) plays a central role in pituitary tumorigenesis, but PTTG protein expression is poorly documented and its relationship with tumour cell proliferation and the prognosis of pituitary adenomas is unclear. AIM: The aim of this study was to evaluate the immunohistochemical expression of PTTG and Ki-67 in 45 human pituitary adenomas according to the tumour histotype, aggressiveness and persistence/recurrence status. PATIENTS AND METHODS: The tumours comprised 37 macroadenomas and 8 microadenomas. Twenty patients experienced disease persistence or recurrence after transsphenoidal surgery. Disease recurrence was observed in 16 patients, 8-72 months after surgery. RESULTS: No PTTG or Ki-67 expression was detected in normal pituitary tissue. In pituitary adenomas, tumour nuclei were positive for PTTG and Ki-67 in 89 and 98% of samples, respectively, and there was a strong correlation between the expression of the two proteins (P < 0.001). By the ROC curves method, a PTTG score of 3.3% was the best cut-off for distinguishing between recurrent and nonrecurrent pituitary adenomas (P < 0.05; sensitivity 60%; specificity 76%). A 2.9% cut-off was obtained for both PTTG (P < 0.01; sensitivity 77%; specificity 71%) and Ki-67 (P < 0.05; sensitivity 85%; specificity 64%) among patients with more than 1 year of follow-up. Neither PTTG nor Ki-67 expression was influenced by the maximal tumour diameter, tumour grade, age, gender or presurgical medical treatment. Both PTTG and Ki-67 tumour score > 2.9% identified a subgroup of patients with a significantly higher recurrence-free interval (P < 0.01). By multivariate analysis, a > 2.9% Ki-67 tumour score was the best predictor of pituitary tumour persistence/recurrence after surgery (chi(2) = 8.2, P < 0.01). CONCLUSION: PTTG is expressed in approximately 90% of pituitary tumours of different histotypes but with a high variability from one case to another. As expected, PTTG expression parallels that of Ki-67 and both are correlated to a more aggressive behaviour. However, a 2.9% Ki-67 cut-off proved to be the most reliable biological marker for predicting the recurrence potential of these tumours, when an adequate postsurgical follow-up is considered.
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Adenoma/genética , Regulación Neoplásica de la Expresión Génica , Proteínas de Neoplasias/genética , Recurrencia Local de Neoplasia/genética , Neoplasias Hipofisarias/genética , Adenoma/patología , Adenoma/cirugía , Adulto , Anciano , Biomarcadores de Tumor/análisis , Distribución de Chi-Cuadrado , Femenino , Expresión Génica , Humanos , Inmunohistoquímica/métodos , Antígeno Ki-67/análisis , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/cirugía , Pronóstico , Curva ROC , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Securina , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Circulating oxidized LDL (ox-LDL) is associated with clinical manifestations of atherosclerosis. The aim of the study was to investigate the concentrations of ox-LDL in HIV-infected patients under antiretroviral therapy with (HIV-LD) or without (HIV-nLD) HIV-related lipodystrophy. METHOD: A total of 44 HIV-infected men were enrolled in the study. Half of them had HIV-LD. The control group included 12 age- and body mass index (BMI)-matched HIV-uninfected men. Ox-LDL concentration and C-reactive protein level were determined. Insulin sensitivity was measured using the homeostasis model assessment (HOMA-IR). LD was assessed by using a validated score calculated from clinical and biological data. RESULTS: HIV-infected patients had significantly higher ox-LDL concentrations when compared to HIV-negative controls (0.8 +/- 0.3 mg/dL vs. 0.60 +/- 0.1 mg/dL; p = .007). HIV-LD patients had significantly higher ox-LDL concentrations than HIV-nLD patients (0.91 +/- 0.38 and 0.69 +/- 0.16; p = .04). In HIV-LD patients, current therapy with protease inhibitors (PIs); duration of PI therapy; HOMA-IR; and time exposure to stavudine, efavirenz, ritonavir, saquinavir, and amprenavir were significantly higher than in HIV-nLD patients. In multivariate analysis, time exposures to stavudine and ox-LDL concentration were independently related to lipodystrophy. CONCLUSION: The high concentration of ox-LDL was found in HIV-infected patients under antiretroviral therapy, especially in those with lipodystrophy.
Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Lipoproteínas LDL/sangre , Oxidación-Reducción , Infecciones por VIH/sangre , Síndrome de Lipodistrofia Asociada a VIH/sangre , Síndrome de Lipodistrofia Asociada a VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVE: Plasma concentration of adiponectin is positively correlated with high-density lipoprotein (HDL) cholesterol level. However, the role of adiponectin on HDL metabolism remains unknown. This prompted us to perform an in vivo kinetic study of apoA-I, the main apolipoprotein of HDL, using stable isotopes, in 22 subjects with a wide range of plasma adiponectin, including 11 patients with metabolic syndrome (8 with type 2 diabetes, 3 without type 2 diabetes) and 11 normal individuals. METHODS AND RESULTS: In the 22 studied subjects, plasma adiponectin levels ranged from 2.57 to 14.44 microg/mL and apoA-I fractional catabolic rate (FCR) values ranged from 0.142 to 0.340 day(-1). A strong negative correlation was found between adiponectin and apoA-I FCR (r=-0.66, P<0.001) in the whole studied population and, to a similar extent, in patients with metabolic syndrome (r=-0.73, P=0.010) and normal subjects (r=-0.68, P=0.020), separately. In multivariable analysis, apoA-I FCR was associated negatively with adiponectin (P=0.005) and positively with HDL triglycerides/cholesterol ratio (P=0.006), but not with age, sex, body mass index (BMI), waist circumference, plasma triglycerides, HDL cholesterol, fasting glycemia, and QUICKI. Both adiponectin and HDL triglycerides/cholesterol ratio explained 62% of the variance of apoA-I FCR and adiponectin on its own explained 43%. CONCLUSIONS: Our kinetic study shows a strong negative correlation between adiponectin and apoA-I FCR, which can explain the positive link between HDL cholesterol and adiponectin. This association is independent of obesity, insulin resistance, and the content of triglycerides within HDL particles. These data suggest that adiponectin may have a direct role on HDL catabolism.
Asunto(s)
Adiponectina/metabolismo , Apolipoproteína A-I/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Síndrome Metabólico/metabolismo , Adiponectina/sangre , Adulto , Anciano , Estudios de Casos y Controles , Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Femenino , Humanos , Cinética , Lipoproteínas HDL/sangre , Masculino , Síndrome Metabólico/sangre , Persona de Mediana Edad , Análisis Multivariante , Triglicéridos/sangreRESUMEN
OBJECTIVES: It has been shown that the HCV-core protein reduces the activity of microsomal triglyceride transfer protein (MTP) and could lead to steatosis in HCV-infected patients. The aim of our study was to investigate the influence of a functional polymorphism in the promoter region of the MTP gene (493G/T) on the development of HCV-related steatosis. METHODS: Eighty-six chronic hepatitis C patients were studied to assess: the effects of body mass index, age, HCV genotype, and 493G/T MTP polymorphism on steatosis. RESULTS: Steatosis was observed in 39 patients (45.3%). The 493G/T MTP polymorphism were not related to the development of steatosis. CONCLUSION: The functional G/T MTP polymorphism do not seem to play any role in the development of steatosis in chronic hepatitis C.