RESUMO
BACKGROUND: Observational studies suggest that higher levels of 25-hydroxyvitamin D3 (25(OH)D) are associated with a reduced risk of colorectal cancer and improved survival of colorectal cancer patients. However, the influence of vitamin D status on cancer recurrence and survival of patients with stage III colon cancer is unknown. PATIENTS AND METHODS: We prospectively examined the influence of post-diagnosis predicted plasma 25(OH)D on outcome among 1016 patients with stage III colon cancer who were enrolled in a National Cancer Institute-sponsored adjuvant therapy trial (CALGB 89803). Predicted 25(OH)D scores were computed using validated regression models. We examined the influence of predicted 25(OH)D scores on cancer recurrence and mortality (disease-free survival; DFS) using Cox proportional hazards. RESULTS: Patients in the highest quintile of predicted 25(OH)D score had an adjusted hazard ratio (HR) for colon cancer recurrence or mortality (DFS) of 0.62 (95% confidence interval [CI], 0.44-0.86), compared with those in the lowest quintile (Ptrend = 0.005). Higher predicted 25(OH)D score was also associated with a significant improvement in recurrence-free survival and overall survival (Ptrend = 0.01 and 0.0004, respectively). The benefit associated with higher predicted 25(OH)D score appeared consistent across predictors of cancer outcome and strata of molecular tumor characteristics, including microsatellite instability and KRAS, BRAF, PIK3CA, and TP53 mutation status. CONCLUSION: Higher predicted 25(OH)D levels after a diagnosis of stage III colon cancer may be associated with decreased recurrence and improved survival. Clinical trials assessing the benefit of vitamin D supplementation in the adjuvant setting are warranted. CLINICALTRIALS.GOV IDENTIFIER: NCT00003835.
Assuntos
Neoplasias do Colo/patologia , Recidiva Local de Neoplasia , Vitamina D/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/sangue , Neoplasias do Colo/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
The experiment was set up in an area of 9 ha that was split into 4 plots: in plot 1 the row spacing was 12 cm and the seeding rate was 10 kg; in plot 2 the row spacing was 24 cm and the seeding rate was 10 kg; in plot 3 the row spacing was 24 cm and the seeding rate was 8 kg; in plot 4 the row spacing was 12 cm and the seeding rate was 8 kg. After the weed surveying, the total weed coverage was established as follows: in plot 1 the total weed coverage was 11.34%, in plot 2 it was 12.3%, in plot 3 it was 18%, and in plot 4 the total weed coverage was 15%. Based on the weed survey, on the test area the following dicotyledon weeds belonging to the T4 Raunkiaer plant life-form category occupied the highest percentage: heal-all, black-bindweed, goosefoot. The proportion of the perennial dicotyledons: field bindweed (G3), tuberous pea (G1), white campion (H3) was negligible. In all four cases the weed control was executed using the same herbicide in the same doses and with regard to the weed species it showed the same level of efficiency. The smaller row spacing and higher seeding rate has a beneficial effect on the weed suppressing capacity of the crop, the crop's weed suppressing capacity is better and the development of the weeds becomes worse.
Assuntos
Produtos Agrícolas/crescimento & desenvolvimento , Herbicidas/farmacologia , Magnoliopsida/efeitos dos fármacos , Plantas Daninhas/efeitos dos fármacos , Controle de Plantas Daninhas/métodos , Magnoliopsida/crescimento & desenvolvimento , Plantas Daninhas/crescimento & desenvolvimentoRESUMO
Pituitary blastoma, a recently described tumor of the neonatal pituitary, exhibits differentiation to Rathke epithelium and adenohypophysial cells of folliculostellate and secretory type, a reflection of arrested pituitary development and unchecked proliferation (Scheithauer et al. in Acta Neuropathol 116(6):657-666, 2008). Herein, we report the pathologic features of three additional cases, all ACTH-producing. One involved a 9-month-old male presenting with progressive right ophthalmoplegia, MRI findings of a large suprasellar mass with cavernous sinus invasion, and elevated plasma ACTH levels. The second was nonfunctioning and occurred in a 13-month-old female with right third nerve palsy. The third had been previously published as a "pituitary adenoma" in a 2-year-old female (Min et al. in Pathol Int 57(9):600-605, 2007). The subtotally resected tumors were subject to histochemical, immunohistochemical and, in two cases, ultrastructural study. Histologically, the complex tumors consisted of glands of varying from rosettes to glandular structures resembling Rathke epithelium, small undifferentiated-appearing cells (blastema), and large secretory cells. Mucin-producing goblet cells were noted in case 3. Cell proliferation was high in two cases and low in case 3. Immunoreactivity of the secretory cells included synaptophysin, chromogranin, various keratins and, to a lesser extent, ACTH and beta endorphin. MGMT immunolabeling was 40-60%. Mitotic activity was moderate to high in cases 1 and 2 and was low in case 3. The same was true for MIB-1 labeling. Germ cell markers were lacking in all cases. One tumor ultrastructurally consisted of three cell populations including (a) small, polyhedral, primitive-appearing cells (blastema) with scant cytoplasm, abundant glycogen and few organelles, (b) folliculostellate cells and (c) large corticotroph cells containing rough endoplasmic reticulum, golgi membranes, spherical, 150-400 nm secretory granules and occasional perinuclear, intermediate filament bundles. A second example (case 3) lacked a blastema and glandular component. The clinical and morphologic features of our three cases were those of pituitary blastoma. The finding of cellular elements of adenohypophysial development is consistent with a diagnosis of pituitary blastoma and aligns it with blastomas of other organs. It also suggests an underlying specific genetic abnormality. Marked variations in cellular proliferative activity suggest blastomas occur in low- and higher-grade form. Variable MGMT reactivity suggests an incomplete response to temozolomide therapy. Literature regarding similar morphologically complex, infantile, Cushing disease-associated lesions is briefly reviewed.
Assuntos
Adenoma Hipofisário Secretor de ACT/patologia , Adenoma/patologia , Neoplasias Complexas Mistas/patologia , Neoplasias Embrionárias de Células Germinativas/patologia , Hipófise/patologia , Neoplasias Hipofisárias/patologia , Pré-Escolar , Feminino , Humanos , Lactente , MasculinoRESUMO
A 69-year-old woman presented with visual disturbance. Perimetry testing revealed a bitemporal hemianopia. Brain MRI demonstrated a 2.2-cm gadolinium-enhancing pituitary mass. Previously she had been treated for hypothyroidism, hypertension, and dyslipidemia. She had hyperprolactinemia. Endoscopic transsphenoidal debulking improved her visual field defects. Histology showed a chromophobic adenoma. Electron microscopy showed elongated, polar cells with long, slender processes. The small uniform secretory granules were peripherally disposed, collecting heavily within cell processes. Based on electron microscopical characteristics the tumor is consistent with an ACTH-negative female gonadotroph adenoma. The parent cell of this rare variant of a pituitary adenoma is yet unknown.
Assuntos
Adenoma/ultraestrutura , Neoplasias Hipofisárias/ultraestrutura , Corpos Polares/ultraestrutura , Adenoma/complicações , Idoso , Células Cultivadas , Feminino , Gonadotrofos/patologia , Hemianopsia/etiologia , Humanos , Microscopia Eletrônica , Neoplasias Hipofisárias/complicaçõesRESUMO
A carotenoid-less Phaffia rhodozyma mutant (MCP 325) exhibited significantly higher resistance to oxidative stressors such as menadione, H2O2 and K2Cr2O7 than its astaxanthin-producing parental strain (MCP 324). The absence of carotenoids in the mutant did not explain this phenomenon. The cause of the decreased superoxide, hydroxyl radical and glutathione contents, the increased peroxide concentration and the elevated specific activity of catalase under uninduced conditions may be a second mutation. Peroxide treatment induced specific catalase activity in the mutant but not in the parental strain. Regulation of these processes led to the result that, in spite of the mutations, the two strains exhibited the same multiplication rate and generation time.
Assuntos
Basidiomycota/genética , Basidiomycota/fisiologia , Mutação/genética , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , Catalase/metabolismo , Regulação Fúngica da Expressão Gênica/genética , Regulação Fúngica da Expressão Gênica/fisiologia , Glutationa/metabolismo , Peróxidos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismoRESUMO
Lymphangiomas are uncommun congenital malformations of the lymphatic system, that involve the skin and subcutaneous tissues. Of the several types of treatment, surgical excision has been the preferred. There is a high recurrence rate because lymphangiomas tend to infiltrate the surrounding tissues. The bleomycin is a cytotoxic antitumoral antibiotic, that causes modifications of DNA. It has been also successfully used in intralesional injection treatment of cystic hygromas and haemangiomas, based specifically on a high sclerosing effect on vascular endothelium. We report the cases of five patients, with congenital lymphangioma, localized on the leg, in cervical and latero-thoracal region, treated with repeated intralesional bleomycin injections. The treatment indication was given by the location of this lesions and the infiltration of the surrounding vital tissues, that made the complete surgical excision impossible. Intralesional injection of bleomycin into the lymphangiomas was given at a dose, not exceeding 0,5 mg/kg of body weight, at intervals of 4 weeks. Complete resolution (n = 4) or significant improvement (n = 1) occurred in all patients treated. No other treatment was needed. We didn't notice local or general adverse effects. With this method we set the purpose to treat effectively this congenital malformations, obviating the need for invasive primary surgery or systemic treatment regimens. Toward other methods, intralesional bleomycin injections have a minimal risk of side effects (ulceration, pulmonary fibrosis).
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Bleomicina/uso terapêutico , Linfangioma/tratamento farmacológico , Linfangioma/patologia , Neoplasias de Tecido Vascular/tratamento farmacológico , Neoplasias de Tecido Vascular/patologia , Antibióticos Antineoplásicos/administração & dosagem , Bleomicina/administração & dosagem , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Injeções Intralesionais , Perna (Membro)/patologia , Masculino , Pescoço/patologia , Parede Torácica/patologia , Resultado do TratamentoRESUMO
INTRODUCTION: Increased oxidative/nitrative stress is characteristic not only in pathologic, but also in healthy pregnancy. High uterine artery pulsatility index (UtAPI) at the end of the first trimester is associated with altered placentation and elevated risk for adverse pregnancy outcomes. We aimed to examine the relationship of systemic oxidative/nitrative stress and uterine artery pulsatility index in the first trimester and their correlation to pregnancy outcomes. MATERIAL AND METHODS: Healthy pregnant women were recruited at 12-13th gestational week ultrasound examination; UtAPI was determined by color Doppler ultrasound. Patients were divided into high (UtAPI ≥ 2.3) (n = 30) and low (n = 31) resistance groups, and pregnancies were followed until labor. Systemic oxidative/nitrative stress was estimated by measuring total peroxide level, total antioxidant capacity and nitrotyrosine level. RESULTS: Plasma total peroxide level was significantly lower (2,510 ± 39 µM vs. 2,285 ± 59 µM), total antioxidant capacity was higher (781 ± 16 mM CRE vs. 822 ± 13 mM CRE) in the high UtAPI group, which were accompanied by lower birth weight (3,317 ± 64 vs. 3,517 ± 77 g, P < 0.05). Plasma total peroxide level showed a negative correlation (by Pearson) to UtAPI (P < 0.01) and positive correlation to birth weight (P < 0.05). CONCLUSIONS: According to our results, lower systemic oxidative stress showed correlation with high UtAPI measured between the 12-13th weeks of gestation. We also found significant differences in the birth weight of healthy newborns; therefore it is worth examining this relationship in pathological pregnancies.
Assuntos
Estresse Oxidativo/fisiologia , Gravidez/fisiologia , Artéria Uterina/fisiologia , Adulto , Biomarcadores/sangue , Velocidade do Fluxo Sanguíneo , Feminino , Humanos , Recém-Nascido de Baixo Peso/fisiologia , Recém-Nascido , Estudos Prospectivos , Artéria Uterina/metabolismoRESUMO
Polycystic ovary syndrome (PCOS) is associated with elevated cardiovascular risk. Early vascular dysfunction may lead to the development of cardiovascular disease in PCOS. Vitamin D deficiency (VDD) is a common comorbidity of PCOS that contributes to the pathogenesis of the disease and its complications. Both PCOS and VDD are accompanied by increased oxidative stress that may be involved in the arising vascular dysfunction. We aimed to investigate the role of vitamin D status on aortic function. PCOS was induced by an 8-week-long transdermal testosterone treatment of female rats, and low and adequate vitamin D status was achieved by dietary means. Contraction and relaxation abilities of isolated aortic segments were measured by myograph. Resorcin-fuchsin staining and immunohistochemical labeling of 3-nitrotyrosine were performed. No difference was shown in the norepinephrine-induced contraction of the aortas of different groups, whereas we detected reduced acetylcholine- and insulin-evoked relaxation in VDD groups. A lower level of resorcin-fuchsin staining and elevated 3-nitrotyrosine immunostaining was observed in VDD. In our study, we demonstrated early endothelial dysfunction in VDD PCOS rat model. Vitamin D supplementation could prevent vascular disturbances, while VDD itself damaged endothelium-dependent vasorelaxation and induced nitrative stress.
Assuntos
Aorta/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Vitamina D/farmacologia , Animais , Aorta/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Contração Muscular/efeitos dos fármacos , Ratos Wistar , Coloração e RotulagemRESUMO
UNLABELLED: Vascularization is a prerequisite of tumor growth, invasion and metastasis. In the present work, microvessel density was assessed by quantitating using two different endothelial cell biomarkers, endoglin (CD-105) and CD-34. Fifty endocrinologically active and 36 clinically nonfunctioning pituitary adenomas, all surgically resected, as well as 10 autopsy-derived normal adenohypophyses were investigated by immunohistochemistry. The results showed that in every pituitary adenoma type endoglin, an assumed biomarker of proliferating endothelial cells, immunostained fewer vessels than CD-34 which revealed immunopositivity in all capillaries. Differences in endoglin versus CD-34 immunoexpression indicate varying degrees of vascularity in pituitary adenoma subtypes. The low levels of endoglin immunoexpression in pituitary tumors exposed to long-acting somatostatin analogs and dopamine agonists are consistent with the view that these agents inhibit angiogenesis. KEYWORDS: immunohistochemistry, endoglin, CD34, microvascular density, angiogenesis, pituitary.
Assuntos
Adenoma/irrigação sanguínea , Antígenos CD34/análise , Antígenos CD/análise , Hipófise/irrigação sanguínea , Neoplasias Hipofisárias/irrigação sanguínea , Receptores de Superfície Celular/análise , Adenoma/química , Endoglina , Humanos , Imuno-Histoquímica , Microvasos/química , Neoplasias Hipofisárias/químicaRESUMO
AIM/HYPOTHESIS: Postpandrial hyperglycaemia is a significant risk factor for the development of macrovascular diseases. There is no clear agreement in the field whether these alterations result from hyperglycaemic episodes or from exaggerated alterations ('glycaemic swings') in blood glucose. We compared the effect of stable high glucose with a model of poorly maintained insulin-controlled diabetes (on average lower glucose, but with large glycaemic swings) on the development of endothelial dysfunction in rats. METHODS: Intermediate- or long-acting insulin was used to reduce mean blood glucose levels. One group of animals had stable low glucose levels, while animals in the other group exhibited rapid changes ('swings') in their blood glucose concentration. Acetylcholine-induced endothelium-dependent vascular relaxation of the thoracic aorta was measured. Immunohistochemistry, western blot analysis and flow cytometry were used to determine nitrotyrosine formation and poly(ADP-ribose) accumulation in the aorta, in circulating leucocytes and in bone marrow cells. RESULTS: Steady normalisation of blood glucose levels (a model of well-controlled diabetes) protected against the development of endothelial dysfunction, poly(ADP-ribose) polymerase (PARP) activation and nitrotyrosine production. However, impairment of endothelium-dependent relaxation was found in the animals undergoing glycaemic swings, even though the fructosamine levels in these animals were lower than in the untreated diabetic rats. This was associated with elevated PARP activation in the aorta and in bone marrow cells that was similar to or even more pronounced than that seen in the untreated diabetic animals. CONCLUSIONS/INTERPRETATION: Large glycaemic swings exert deleterious cardiovascular effects in diabetes mellitus, in part via enhanced activation of the PARP pathway.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Endotélio Vascular/fisiopatologia , Poli(ADP-Ribose) Polimerases/metabolismo , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiopatologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/enzimologia , Ativação Enzimática , Citometria de Fluxo , Hipoglicemiantes/uso terapêutico , Técnicas In Vitro , Insulina de Ação Prolongada/uso terapêutico , Cinética , Leucócitos/fisiologia , Masculino , Ratos , Ratos Wistar , Estresse MecânicoRESUMO
AIMS/HYPOTHESIS: Increased oxidative-nitrosative stress, poly(ADP-ribose) polymerase (PARP) activation and subsequent cellular damage play important roles in the complications of both diabetes mellitus and pregnancy. Our aim was to investigate nitrative stress and PARP activity levels during normal and gestational diabetic (GDM) pregnancy in both maternal and fetal tissues. METHODS: Blood samples were collected during pregnancy (weeks 16-29 and 36-40), and placental and umbilical cord tissues were harvested after delivery from healthy volunteers and GDM patients subjected to a carbohydrate-restricted diet or insulin treatment. Immunohistochemical staining was performed on leucocytes and tissue sections using anti-nitrotyrosine (NT), anti-poly(ADP-ribose) (PAR) and anti-apoptosis inducing factor antibodies. RESULTS: In healthy pregnancies the intensity of NT and PAR staining of leucocytes correlated positively with gestational week (R (2) = 0.43, p < 0.01 and R (2) = 0.49, p < 0.001, respectively). In patients on a carbohydrate-restricted diet PAR staining was already strong in weeks 16-29 (p < 0.001 vs control) and did not increase further. In weeks 16-29 there was a correlation between PAR staining and the 2 h value of the oral glucose tolerance test (R (2) = 0.49, p < 0.001). Patients with the highest level of leucocyte PARP activity later required insulin therapy, which decreased the intensity of NT and PAR staining. Placental and umbilical cord tissues also had a higher level of nitrative stress markers in GDM pregnancies, but the highest level of PARP activity was observed after insulin therapy. CONCLUSIONS/INTERPRETATION: Continuous elevation of tyrosine nitration and PARP activation may be considered physiological during pregnancy. However, the high level of PARP activity in early pregnancy may signal the subsequent development of severe GDM.
Assuntos
Diabetes Gestacional/enzimologia , Poli(ADP-Ribose) Polimerases/metabolismo , Gravidez/fisiologia , Adulto , Peso ao Nascer , Glicemia/análise , Índice de Massa Corporal , Diabetes Gestacional/sangue , Diabetes Gestacional/tratamento farmacológico , Dieta para Diabéticos , Ativação Enzimática , Feminino , Teste de Tolerância a Glucose , Humanos , Hipoglicemiantes/uso terapêutico , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Insulina/uso terapêutico , Leucócitos/citologia , Trabalho de Parto Prematuro , Paridade , Gravidez/sangue , Valores de Referência , Aumento de PesoRESUMO
BACKGROUND: Macroadenomas represent 50% of pituitary tumours and are often (30%) nonfunctioning. Their immunophenotype suggests differentiation toward a specific pituitary cell line. A substantial proportion of tumours with particularly aggressive behaviour are so called 'silent subtype 3 adenoma'. Its diagnosis requires ultrastructural confirmation. Although once included among silent corticotroph adenomas, this aggressive, morphologically distinctive tumour is now recognized as a major form of plurihormonal adenoma and, in fact, some patients might present with clinical hormonal excess. The cytogenesis and pathobiology of silent subtype 3 adenomas is unsettled. OBJECTIVE: We undertook a systematic clinicopathologic examination of the Mayo Clinic experience with this poorly understood tumour. DESIGN: This retrospective, single institution study found 27 confirmed examples of silent subtype 3 adenoma, a frequency of 0.9% of adenomas. Despite histologic and immunophenotypic variation, their ultrastructural features were diagnostic and the sole basis for case inclusion. RESULTS: The study group was comprised of 16 men (59%) and 11 women (41%); two patients (7%) had definitive diagnosis of multiple endocrine neoplasia type 1 (MEN1). Three tumours (11%) were discovered incidentally. Nine patients each (38%) presented with headaches or visual field loss. Endocrine hyperfunction was noted in eight cases (30%), including GH excess in five (19%) and clinically significant PRL elevation in three (11%). Hypogonadism was noted in 17 cases (63%) and growth arrest in one (4%). All tumours were macroadenomas; 16 (60%) showed radiographic evidence of invasion. Most tumours were plurihormonal, featuring immunoreactivity for PRL (17), GH (15), TSH (16) or ACTH (3); only one lesion was immunonegative. Although a gross total resection was achieved in 19 cases (70%), re-operation for recurrence(s) was required in seven of these (37%). Follow-up (mean, 69 months) showed a high (59%) rate of persistent or recurrent of tumour. Overall, 14 patients (54%) underwent radiotherapy after surgical treatment: three patients (12%) for substantial residual tumour, eight (31%) as adjuvant therapy and three (12%) for tumour regrowth. CONCLUSION: Silent subtype 3 adenoma, a plurihormonal tumour, is rare and aggressive in nature. This adenoma must be considered in the differential of often clinically nonfunctioning but plurihormonal adenomas featuring variable cytologic atypia. Electron microscopy is required for confirmation of the diagnosis. The cytogenesis of silent subtype 3 adenoma remains unsettled.
Assuntos
Neoplasias Hipofisárias/patologia , Adulto , Idoso , Feminino , Hormônios/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Minnesota , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/diagnóstico por imagem , Radiografia , Estudos Retrospectivos , Adulto JovemRESUMO
We report a rapidly recurring folliculostellate cell tumor of the adenohypophysis in a 63-year-old woman. Morphologically the tumor had the typical appearance of a spindle cell oncocytoma of the adenohypophysis. It recurred within 5 months of selective transsphenoidal resection, requiring a second transsphenoidal operation followed by radiation therapy. The spindle cell oncocytoma (SCO) of the adenohypophysis is a relatively recently described entity and a new addition to the fourth edition of the WHO Classification of Tumors of the Central Nervous System. In our case, the ultrastructural features were significantly different from those so far described in SCO, in that tumor cells formed a network of structures indistinguishable from pituitary follicles. In addition, a minority of tumor cells exhibited endocrine differentiation.
Assuntos
Adenoma Oxífilo/ultraestrutura , Neoplasias Hipofisárias/ultraestrutura , Adenoma Oxífilo/fisiopatologia , Biomarcadores Tumorais/análise , Feminino , Humanos , Imuno-Histoquímica , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Neoplasias Hipofisárias/fisiopatologiaRESUMO
OBJECTIVE AND IMPORTANCE: Pituitary adenomas producing primarily FSH and to a lesser extent GH, LH, alpha-subunit, TSH and PRL without clinical or laboratory evidence of increased hormone release have not previously been reported. Our aim was to obtain some insight into the possible cytogenesis of this unusual tumor. CLINICAL PRESENTATION: A 65-year-old woman presented with headaches. Magnetic resonance imaging (MRI) demonstrated a sellar mass. Pituitary hormone assays showed normal blood levels. The tumor was removed by the transsphenoidal approach. RESULT: By light microscopy, the adenoma was chromophobic, weakly PAS-positive, and immunoreactive mainly for FSH (85%) and to a lesser extent for GH (30%), LH (15%), alpha-subunit (3%), TSH (2%), and PRL (1%). Although double immunostaining showed hormone reactivities to be localized largely in separate distinct cells, the tumor was ultrastructurally monomorphous, i.e., consisted of a single-cell type, resembling gonadotrophs. CONCLUSION: The cytogenesis of plurihormonal pituitary adenomas is not fully understood. Further investigations are required to clarify the basis for their plurihormonality despite an ultrastructural gonadotroph phenotype.
Assuntos
Adenoma/metabolismo , Adenoma/patologia , Gonadotrofos/metabolismo , Gonadotrofos/patologia , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Adenoma/fisiopatologia , Idoso , Feminino , Hormônio Foliculoestimulante/biossíntese , Hormônio do Crescimento/biossíntese , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Neoplasias Hipofisárias/fisiopatologia , Prolactina/biossíntese , Tireotropina/biossínteseRESUMO
This review discusses the pathophysiology of acromegaly. Acromegaly has been classified in this paper into distinct entities based on etiology, ultrastructural features of the pituitary, and cytogenesis. This classification has been proposed based on clinical signs, immunoperoxidase techniques, transmission electromicroscopy and immunoelectron microscopy. Pituitary causes of acromegaly include densely granulated adenomas, sparsely granulated adenomas, mixed growth hormone and prolactin cell adenomas, acidophil stem cell adenomas, mammosomatotroph cell adenomas, and pleurihormonal adenomas. GH cell hyperplasia and GH cell carcinoma are also discussed. Extrapituitary causes of acromegaly include eutopic GH cell adenoma in the sphenoid sinus or parapharyngeal region and excess GHRF secretion which may be eutopic or ectopic. The pathological, clinical, and biochemical evidence in favor of a pituitary or hypothalamic etiology of acromegaly has been reviewed. Finally, a multistage theory of GH cell tumorigenesis has been proposed as a model in an attempt to unify the genetic, environmental and biochemical factors implicated in the pathogenesis of acromegaly.
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Acromegalia/fisiopatologia , Acromegalia/complicações , Acromegalia/patologia , Adenoma/patologia , Adenoma/fisiopatologia , Hormônio do Crescimento/metabolismo , Humanos , Adeno-Hipófise/metabolismo , Adeno-Hipófise/fisiopatologia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/etiologia , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologiaRESUMO
The normal infundibulum and neurohypophysis consist entirely of neuronal processes, the neuronal cell bodies of which lie within the supraoptic and paraventricular nuclei of the hypothalamus and supportive glial cells or pituicytes. The finding of neurons within the neurohypophysis is exceedingly rare, as are ganglion cell tumors at this site. In this paper, we report a ganglion cell tumor of the neurohypophysis found incidentally at autopsy. Despite chronic hypertension and the finding of some vasopressin immunoreactivity in lesional neurons, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was excluded on the basis of normal serum sodium levels. The morphologic and immunohistochemical features of the tumor are presented, cytogenetic considerations are discussed, and literature regarding neuronal lesions of the pituitary gland is reviewed.
Assuntos
Ganglioglioma/patologia , Neuro-Hipófise/patologia , Neoplasias Hipofisárias/patologia , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Encéfalo/patologia , Feminino , Humanos , Imuno-Histoquímica , Síndrome de Secreção Inadequada de HAD/diagnóstico , Síndrome de Secreção Inadequada de HAD/patologia , Hipófise/patologia , Sódio/sangueRESUMO
PurposeThe purpose of the study was to report the outcome of posterior approach white-line advancement surgery for severe involutional aponeurotic ptosis.Patients and methodsThis was a retrospective review of an interventional case series of all patients undergoing surgery for severe involutional aponeurotic ptosis during a 42-month period at a single center. The inclusion criteria were severe involutional ptosis (upper eyelid margin reflex distance (MRD) ≤1 mm) undergoing posterior approach surgery. There was minimum 3-month follow-up. The main outcome measures were type of ptosis (primary or recurrent), preoperative margin reflex distance, levator function and eyelid skin crease height, presence of visible iris sign (VIS), documented unusual intraoperative findings, postoperative complications, and follow-up time.ResultsOf the 836 procedures for ptosis, 122 procedures (76 patients) met the inclusion criteria for this study. Mean postoperative follow-up was 28 (median 18, range 12-98) weeks. Success rates were 80.3% (98/122) overall, 81.5% (66/81) in the non-VIS group, and 78% (32/41) in the VIS group. There was no significant difference between the two groups (P=0.411). Failures were due to undercorrection, with <2 mm MRD in 75% (18/24), overcorrection with >4.5 mm MRD in 16.7% (4/24), and inter-eyelid height asymmetry of >1 mm in 8.3% (2/122).ConclusionsOutcomes of ptosis surgery for severe aponeurotic ptosis using a posterior approach white-line advancement are comparable to, and possibly better than, anterior approach in eyelids with VIS.
Assuntos
Blefaroplastia/métodos , Blefaroptose/cirurgia , Pálpebras/cirurgia , Músculos Oculomotores/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Blefaroptose/fisiopatologia , Criança , Movimentos Oculares/fisiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Músculos Oculomotores/fisiopatologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Reino Unido/epidemiologia , Adulto JovemRESUMO
A 21-yr-old woman with Turner's syndrome presented with signs and symptoms of acromegaly. The serum growth hormone (GH) (95+/-9.4 ng/ml; mean+/-SEM) and somatomedin C (11 U/ml) levels were elevated, and an increase in GH levels after glucose instead of normal suppression, increase after thyrotropin-releasing hormone (TRH) administration instead of no change, and decrease after dopamine administration instead of stimulation were observed. The pituitary fossa volume was greater than normal (1,440 mm(3)) and the presence of a pituitary tumor was assumed. After tissue removal at transsphenoidal surgery, histological study revealed somatotroph hyperplasia rather than a discrete adenoma. Postoperatively, she remained clinically acromegalic and continued to show increased GH and somatomedin levels. A search was made for ectopic source of a growth hormone-releasing factor (GRF). Computer tomographic scan revealed a 5-cm Diam tumor in the tail of the pancreas. Following removal of this tumor, serum GH fell from 70 to 3 ng/ml over 2 h, and remained low for the subsequent 5 mo. Serum somatomedin C levels fell from 7.2 to normal by 6 wk postoperatively. There were no longer paradoxical GH responses to glucose, TRH, and dopamine. Both the medium that held the tumor cells at surgery and extracts of the tumor contained a peptide with GRF activity. The GRF contained in the tumor extract coeluted on Sephadex G-50 chromatography with rat hypothalamic GH-releasing activity. Stimulation of GH from rat somatotrophs in vitro was achieved at the nanomolar range, using the tumor extract. The patient's course demonstrates the importance of careful interpretation of pituitary histology. Elevated serum GH and somatomedin C levels in a patient with an enlarged sella turcica and the characteristic responses seen in acromegaly to TRH, dopamine, and glucose do not occur exclusively in patients with discrete pituitary tumors and acromegaly. This condition can also occur with somatotroph hyperplasia and then revert to normal after removal of the GRF source. Thus, in patients with acromegaly a consideration of ectopic GRF secretion should be made, and therefore, careful pituitary histology is mandatory. Consideration for chest and abdominal computer tomographic scans before pituitary surgery, in spite of their low yield, may be justified.