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PURPOSE: A series of consensus guidelines on medical treatment of acromegaly have been produced in the last two decades. However, little information is available on their application in clinical practice. Furthermore, international standards of acromegaly care have not been published. The aim of our study was to report current standards of care for medical therapy of acromegaly, using results collected through an audit performed to validate criteria for definition of Pituitary Tumor Centers of Excellence (PTCOE). METHODS: Details of medical treatment approaches to acromegaly were voluntarily provided by nine renowned international centers that participated in this audit. For the period 2018-2020, we assessed overall number of acromegaly patients under medical treatment, distribution of patients on different treatment modalities, overall biochemical control rate with medical therapy, and specific control rates for different medical treatment options. RESULTS: Median number of total patients and median number of new patients with acromegaly managed annually in the endocrinology units of the centers were 206 and 16.3, respectively. Median percentage of acromegaly patients on medical treatment was 48.9%. Among the patients on medical treatment, first-generation somatostatin receptor ligand (SRL) monotherapy was used with a median rate of 48.7%, followed by combination therapies with a median rate of 29.3%. Cabergoline monotherapy was used in 6.9% of patients. Pegvisomant monotherapy was used in 7 centers and pasireotide monotherapy in 5 centers, with median rates of 7.9% and 6.3%, respectively. CONCLUSIONS: Current standards of care in PTCOEs include use of first-generation SRLs as the first medical option in about 50% of patients, as recommended by consensus guidelines. However, some patients are kept on this treatment despite inadequate control suggesting that cost-effectiveness, availability, patient preference, side effects, and therapeutic inertia may play a possible role also in PTCOE. Moreover, at odds with consensus guidelines, other monotherapies for acromegaly appear to have a marginal role as compared to combination therapies as extrapolated from PTCOE practice data. Presence of uncontrolled patients in each treatment category suggest that further optimization of medical therapy, as well as use of other therapeutic tools such as radiosurgery may be needed.
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Acromegalia , Neoplasias Hipofisárias , Padrão de Cuidado , Acromegalia/tratamento farmacológico , Acromegalia/terapia , Humanos , Neoplasias Hipofisárias/terapia , Neoplasias Hipofisárias/tratamento farmacológico , Feminino , Masculino , Cabergolina/uso terapêutico , Pessoa de Meia-Idade , AdultoRESUMO
PURPOSE: The Pituitary Society established the concept and mostly qualitative parameters for defining uniform criteria for Pituitary Tumor Centers of Excellence (PTCOEs) based on expert consensus. Aim of the study was to validate those previously proposed criteria through collection and evaluation of self-reported activity of several internationally-recognized tertiary pituitary centers, thereby transforming the qualitative 2017 definition into a validated quantitative one, which could serve as the basis for future objective PTCOE accreditation. METHODS: An ad hoc prepared database was distributed to nine Pituitary Centers chosen by the Project Scientific Committee and comprising Centers of worldwide repute, which agreed to provide activity information derived from registries related to the years 2018-2020 and completing the database within 60 days. The database, provided by each center and composed of Excel® spreadsheets with requested specific information on leading and supporting teams, was reviewed by two blinded referees and all 9 candidate centers satisfied the overall PTCOE definition, according to referees' evaluations. To obtain objective numerical criteria, median values for each activity/parameter were considered as the preferred PTCOE definition target, whereas the low limit of the range was selected as the acceptable target for each respective parameter. RESULTS: Three dedicated pituitary neurosurgeons are preferred, whereas one dedicated surgeon is acceptable. Moreover, 100 surgical procedures per center per year are preferred, while the results indicated that 50 surgeries per year are acceptable. Acute post-surgery complications, including mortality and readmission rates, should preferably be negligible or nonexistent, but acceptable criterion is a rate lower than 10% of patients with complications requiring readmission within 30 days after surgery. Four endocrinologists devoted to pituitary diseases are requested in a PTCOE and the total population of patients followed in a PTCOE should not be less than 850. It appears acceptable that at least one dedicated/expert in pituitary diseases is present in neuroradiology, pathology, and ophthalmology groups, whereas at least two expert radiation oncologists are needed. CONCLUSION: This is, to our knowledge, the first study to survey and evaluate the activity of a relevant number of high-volume centers in the pituitary field. This effort, internally validated by ad hoc reviewers, allowed for transformation of previously formulated theoretical criteria for the definition of a PTCOE to precise numerical definitions based on real-life evidence. The application of a derived synopsis of criteria could be used by independent bodies for accreditation of pituitary centers as PTCOEs.
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Doenças da Hipófise , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/cirurgia , Projetos Piloto , HipófiseRESUMO
BACKGROUND: Dupilumab is an antibody against interleukin-4 receptor α, used in the treatment of atopic dermatitis (AD). OBJECTIVES: To evaluate the efficacy and safety of dupilumab in adult Chinese patients with moderate-to-severe AD. METHODS: In this randomized, double-blind, placebo-controlled, parallel-group, phase III study, conducted between December 2018 and February 2020, patients with AD received dupilumab (300 mg) or placebo once every 2 weeks for 16 weeks, and were followed up for 12 weeks. The primary efficacy endpoint was the proportion of patients with both an Investigator's Global Assessment score of 0-1 and a reduction from baseline of ≥ 2 points at week 16. RESULTS: Overall, 165 patients (mean age 30·6 years; 71·5% male patients) were randomized; 82 patients were randomized to dupilumab and 83 patients were randomized to placebo. At week 16, 26·8% of patients in the dupilumab group and 4·8% of patients in the placebo group achieved the primary endpoint [difference 22·0%, 95% confidence interval (CI) 11·37-32·65; P < 0·001]. Compared with placebo, higher proportions of patients in the dupilumab group achieved ≥ 75% reduction in the Eczema Area and Severity Index score (57·3% vs. 14·5%; difference 42·9%, 95% CI 29·75-55·97; P < 0·001) and had ≥ 3-point (52·4% vs. 9·6%; difference 42·8%, 95% CI 30·26-55·34; P < 0·001) and ≥ 4-point (39·0% vs. 4·8%; difference 34·2%, 95% CI 22·69-45·72; P < 0·001) reductions in weekly average daily peak daily pruritus numerical rating scale scores. The incidence of treatment-emergent adverse events during the treatment period was similar in the two groups. The incidence of conjunctivitis, allergic conjunctivitis and injection site reaction was higher in the dupilumab group than in the placebo group. CONCLUSIONS: In adult Chinese patients, dupilumab was effective in improving the signs and symptoms of AD and demonstrated a favourable safety profile.
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Dermatite Atópica , Eczema , Adulto , Anticorpos Monoclonais Humanizados , China , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Pituitary tumors are common lesions, and they represent the second most frequent primary brain tumor. Their classification has undergone several changes over time. The World Health Organization conducts periodic expert review/consensus meetings and publishes the results as recommendations for changes in classification, based on advances in molecular and genetic advances. This paper summarizes the results of the 2017 WHO Classification, which recommends several important changes. PURPOSE: This paper provides a review of the major changes and issues leading to an understanding of the basis for a new pituitary tumor classification. They include the rejection and modification of prior conceptual and pathological characteristics of these neoplasms. There is also considerable concern related to invasive and recurrent pituitary tumors which follow a less benign course than the typical pituitary adenoma. METHODS: A review of the outcome data for the previously designated "atypical" pituitary tumor category revealed that the former criteria were not adequate to support their ability to predict with accuracy the clinical course of a given tumor. A similar review was accomplished regarding the role of the p53 tumor suppressor mutation. Again, there was no reliable contribution of p53 status to tumor aggressiveness. Other changes have occurred regarding the cytogenetic lineage of the various subtypes of pituitary adenoma. The transcription factors Pit-1, SF-1, and TPit play a major role in determining tumor subtypes and have become part of the classification criteria. RESULTS: These advances now help provide the background for more reliable and consistent classification of pituitary adenomas. Further definition of aggressive characteristics such as cavernous sinus and dural invasion remain to be considered in the quest to make more accurate prognostic projections based on histopathological analysis. CONCLUSIONS: The 2017 WHO Classification of Pituitary Tumors provides a more solid basis for accurate and reliable prognostic assessment of these lesions. Further progress undoubtedly will be made as the recommendations of this update are incorporated in to routine use.
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Adenoma/patologia , Neoplasias Hipofisárias/patologia , Adenoma/classificação , Humanos , Gradação de Tumores , Hipófise/patologia , Neoplasias Hipofisárias/classificação , Organização Mundial da SaúdeRESUMO
AIMS: We evaluated the potential of a nanoparticle (NP) delivery system to improve methods of delivery of candidate peptide-based vaccines for Paratuberculosis in cattle. METHODS AND RESULTS: Peptides derived from Mycobacterium avium subsp. paratuberculosis (Map), and the pro-inflammatory monophosphoryl lipid A (MPLA) were incorporated in polymeric NPs based on poly (d,l-lactide-co-glycolide) (PLGA). The PLGA/MPLA NPs carriers were incubated with macrophages to examine their effects on survival and function. PLGA/MPLA NPs, with and without Map antigens, are efficiently phagocytized by macrophages with no evidence of toxicity. PLGA/MPLA NP formulations did not alter the level of expression of MHC I or II molecules. Expression of TNFα and IL12p40 was increased in Map-loaded NPs. T-cell proliferation studies using a model peptide from Anaplasma marginale demonstrated that a CD4 T-cell recall response could be elicited with macrophages pulsed with the peptide encapsulated in the PLGA/MPLA NP. CONCLUSIONS: These findings indicate PLGA/MPLA NPs can be used as a vehicle for delivery and testing of candidate peptide-based vaccines. SIGNIFICANCE AND IMPACT OF THE STUDY: These results will assist on more in depth studies on PLGA NP delivery systems that may lead to the development of a peptide-based vaccine for cattle.
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OBJECTIVES: To determine if dogs with acute polyradiculoneuritis have lower serum 25-hydroxy vitamin D3 concentration compared to a control group of dogs with idiopathic epilepsy. MATERIALS AND METHODS: Retrospective case-control study of 21 dogs with acute canine polyradiculoneuritis and 21 control dogs with idiopathic epilepsy matched for year and season of presentation from a referral hospital population in the UK. Serum concentration of 25-hydroxy vitamin D3 was compared between groups using Student's t-test. RESULTS: Dogs with acute canine polyradiculoneuritis had significantly lower (P=0·033) serum 25-hydroxy vitamin D3 concentration (87·1 nmol/L ±55·4 nmol/L) compared to a control group with idiopathic epilepsy (113 nmol/L ±66·3 nmol/L). CLINICAL SIGNIFICANCE: The cause and clinical significance of the altered vitamin D status in dogs with acute polyradiculoneuritis are not clear and require further investigation. Our findings pave the way for improved understanding of acute canine polyradiculoneuritis and, potentially, improved clinical management, if a causal role for 25-hydroxy vitamin D3 is defined.
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Calcifediol/sangue , Doenças do Cão/sangue , Polirradiculoneuropatia/veterinária , Vitaminas/sangue , Animais , Estudos de Casos e Controles , Cães , Feminino , Masculino , Polirradiculoneuropatia/sangue , Estudos RetrospectivosRESUMO
Essentials Protease activated receptor-1 (PAR-1) has been proposed to drive cancer progression. Surprisingly, PAR-1 deletion accelerated tumor progression in two distinct experimental settings. PAR-1 deletion was shown to limit the apoptosis of transformed epithelial cells. Thrombin- and activated protein C-mediated PAR-1 activation have unique effects on tumor cell biology. SUMMARY: Background Multiple studies have implicated protease-activated receptor-1 (PAR-1), a G-protein-coupled receptor activated by proteolytic cleavage of its N-terminus, as one target coupling thrombin-mediated proteolysis to tumor progression. Objective To analyze the role of PAR-1 in the setting of two distinct spontaneously developing tumor models in mice. Methods We interbred PAR-1-deficient mice with Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice, which spontaneously develop prostate tumors, and adenomatous polyposis coli Min (APCMin/+ ) mice, which spontaneously develop intestinal adenomas. Results Analyses of TRAMP mice with advanced disease (30 weeks) revealed that PAR-1 deficiency resulted in significantly larger and more aggressive prostate tumors. Prostates collected at an earlier time point (12 weeks of age) revealed that PAR-1 promotes apoptosis in transformed epithelia. In vitro analyses of TRAMP-derived cells revealed that activated protein C-mediated PAR-1 cleavage can induce tumor cell apoptosis, suggesting that tumor cell-intrinsic PAR-1 functions can limit tumor progression. Paralleling results in TRAMP mice, PAR-1-deficient APCMin/+ mice developed three-fold more adenomas than PAR-1-expressing mice, and the adenomas that formed were significantly larger. Moreover, loss of PAR-1 expression was shown to limit apoptosis in transformed intestinal epithelial cells. Conclusions Together, these results demonstrate a previously unrecognized role for PAR-1 in impeding tumor progression in vivo. These results also offer a cautionary note suggesting that long-term PAR-1 inhibition could increase malignancy risk in some contexts.
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Progressão da Doença , Neoplasias Intestinais/metabolismo , Neoplasias da Próstata/metabolismo , Receptor PAR-1/metabolismo , Animais , Apoptose , Transformação Celular Neoplásica , Cruzamentos Genéticos , Deleção de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Tumores Neuroendócrinos/metabolismo , Neoplasias da Próstata/genética , Proteína C/metabolismo , Trombina/metabolismoRESUMO
OBJECTIVES: To investigate whether the development of acute canine polyradiculoneuritis is associated with various putative risk factors. MATERIALS AND METHODS: Retrospective case-control study with conditional logistic regression analysis from a referral hospital population in the UK where controls were matched for year of presentation. RESULTS: Forty-three cases were identified with acute canine polyradiculoneuritis and 86 controls were selected. Jack Russell terriers and West Highland white terriers were found to have a significantly greater odds of developing acute canine polyradiculoneuritis compared to a mixed baseline group of dogs. The odds of developing acute canine polyradiculoneuritis were greater in the autumn and winter compared to spring. Vaccination, rural/urban habitation, sex, neuter status and age were not associated with development of acute canine polyradiculoneuritis in our population of dogs. CLINICAL SIGNIFICANCE: Breed and season were associated with development of acute canine polyradiculoneuritis. However, this is a small sample and so this observation needs confirmation in further studies and other factors may also be involved. Nevertheless, these findings may be important in further understanding the aetiopathogenesis of this condition.
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Doenças do Cão/epidemiologia , Polirradiculoneuropatia/veterinária , Animais , Cruzamento , Estudos de Casos e Controles , Cães , Feminino , Masculino , Polirradiculoneuropatia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Estações do AnoRESUMO
Pituitary adenomas are relatively common intracranial neoplasms that are frequently treated with surgical resection. Rapid visualization of pituitary tissue remains a challenge as current techniques either produce little to no information on hormone-secreting function or are too slow to practically aid in intraoperative or even perioperative decision-making. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) represents a powerful method by which molecular maps of tissue samples can be created, yielding a two-dimensional representation of the expression patterns of small molecules and proteins from biologic samples. In this chapter, we review the use of MALDI MSI, its application to the characterization of the pituitary gland, and its potential applications for guiding the management of pituitary adenomas.
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Biomarcadores/metabolismo , Processamento de Imagem Assistida por Computador/métodos , Espectrometria de Massas/métodos , Imagem Molecular/métodos , Monitorização Intraoperatória/métodos , Neoplasias Hipofisárias/patologia , Animais , Gerenciamento Clínico , Humanos , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/cirurgiaRESUMO
BACKGROUND: Limited information is available about prognostic factors for recovery after spinal cord injury (SCI) to the L4-S3 segments. Previous research suggests that L4-S3 SCI does not have a worse prognosis than T3-L3 SCI. HYPOTHESIS/OBJECTIVES: To elucidate prognostic factors for regaining urinary continence and ambulation in dogs with L4-S3 SCI and compare prognosis to T3-L3 SCI. ANIMALS/METHODS: A retrospective study on 61 nonambulatory dogs with L4-S3 SCI, matched to dogs with T3-L3 SCI, compared 3 weeks after onset. Prognostic factors explored using logistic regression and used for matching: nonchondrodystrophic dogs >15 kg versus dogs that were chondrodystrophic or <15 kg; compressive versus noncompressive lesions; presence versus absence of conscious pain perception (CPP); and lower vs upper motor neuron (LMN/UMN) incontinence. RESULTS: Fewer L4-S3 dogs regained continence compared to T3-L3 dogs (64 vs 85%, P = .0033), but no difference existed for regaining ambulation (66 vs 75%, P = .1306). In L4-S3 SCI dogs, fewer dogs regained continence with loss of CPP (P < .001), LMN incontinence (P = .004), and noncompressive lesions (P = .006). Negative prognostic factors for regaining ambulation included absent CPP (P < .001) and large nonchondrodystrophic breed (P = .022). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with L4-S3 SCI have a poorer short-term prognosis than do dogs with T3-L3 SCI. Dogs with L4-S3 SCI had a poor prognosis with loss of CPP, or noncompressive lesions combined with LMN incontinence. Small-breed or chondrodystrophic dogs with retained CPP, compressive lesions, and UMN incontinence had an excellent prognosis. These findings may help guide decision-making in L4-S3 SCI.
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Doenças do Cão/diagnóstico , Cães/lesões , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/veterinária , Incontinência Urinária/veterinária , Animais , Região Lombossacral/lesões , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Traumatismos da Medula Espinal/diagnóstico , Incontinência Urinária/diagnóstico , Incontinência Urinária/etiologia , CaminhadaRESUMO
The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients.
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Adenoma/classificação , Tumores Neuroendócrinos/classificação , Neoplasias Hipofisárias/classificação , HumanosAssuntos
Neoplasias Encefálicas/diagnóstico , Imageamento por Ressonância Magnética/métodos , Idoso , Alanina/metabolismo , Neoplasias Encefálicas/metabolismo , Colina/metabolismo , Feminino , Glioblastoma/diagnóstico , Glioblastoma/metabolismo , Humanos , Lactatos/metabolismo , Ácido Láctico , Masculino , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/metabolismo , Meningioma/diagnóstico , Meningioma/metabolismoRESUMO
Two models for meningeal neoplasia have been developed in rats using intrathecal injection of 9L gliosarcoma and Walker 256 carcinosarcoma cells. Tumor cells were injected in unanesthetized animals through an indwelling catheter inserted at the cisterna magna to the level of the lumbar enlargement of the spinal cord. Survival of rats was dependent on the number of tumor cells injected. Spread of tumor was quantified by histology using a grading scale, and functional and behavioral changes were measured. Rats injected with 10(6) 9L gliosarcoma cells showed progressive weight loss, flaccid paralysis, and neurogenic bladder dysfunction and had a median survival of 11 days. The tumor frequently grew as a mass compressing the spinal cord. The 9L gliosarcoma tumor cells markedly invaded the Virchow-Robin spaces but exhibited only minimal invasion of the central nervous system parenchyma. The tumor reached the brain by day 10. Rats injected with 2 X 10(5) Walker 256 carcinosarcoma cells showed progressive weight loss and weakness and had a median survival of 6 days. The tumor grew within the leptomeninges in a discontinuous multifocal fashion and reached the brain by day 4. There was extensive invasion of the central nervous system parenchyma by Walker 256 tumor cells along the Virchow-Robin spaces resulting in hemorrhage and necrosis of grey and white matter. Hot plate and tail flick response times were significantly delayed only in the days immediately preceding death of animals with either 9L or Walker 256 tumor and were not good indicators of tumor progression. Loss of motor coordination and failure of the stepping and placing reflex on the other hand showed good correlation with spread of tumor measured histologically. Control animals injected with 0.9% NaCl or with lethally irradiated tumor cells showed no significant weight loss or functional or behavioral changes. The intrathecal 9L gliosarcoma and Walker 256 carcinosarcoma models show different characteristics of human meningeal carcinomatosis and will be used for studies of experimental chemotherapy with intrathecally administered antitumor drugs.
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Carcinoma 256 de Walker/patologia , Modelos Animais de Doenças , Glioma/patologia , Neoplasias Meníngeas/patologia , Animais , Peso Corporal , Feminino , Injeções Espinhais , Transplante de Neoplasias , Paralisia/etiologia , RatosRESUMO
An ordinary least squares (OLS) analysis of the relationship between chlorophyll a (chl a) concentrations and photosynthetic rates at depths of 5 and 25 m at Station ALOHA produced a slope that was only 28% of the mean productivity index at those depths and an intercept at zero chl a that equaled 70% of the mean photosynthetic rate. OLS regression lines are known to produce a slope and intercept that are biased estimates of the true slope and intercept when the explanatory variable, X, is uncontrolled, but in this case the measurement errors and natural variability of the chl a concentrations were much too small to explain the apparent bias. The bias was traceable to the fact that the photosynthetic rates were determined by more than one explanatory variable, a source of variability that is typically overlooked in discussions of OLS bias. Modeling the photosynthetic rates as a function of the product of chl a and surface irradiance produced a much more accurate and realistic description of the data, but the OLS continued to be biased, presumably because the photosynthetic rates were functions of factors in addition to chl a and surface irradiance (e.g., temperature, macronutrients, trace metals, and vitamins). The results underscore the need to recognize that the absence of bias in an OLS when X is not controlled implies that all scatter in the data about the OLS is due to errors in the dependent variable, an unlikely scenario. In most cases, resolution of the bias problem will require identification of the explanatory variables in addition to X that determine the dependent variable.
RESUMO
In November 2003, the Pituitary Society and the European Neuroendocrine Association sponsored a consensus workshop in Seville to address challenging issues in the medical management of acromegaly. Participants comprised 70 endocrinologists and neurosurgeons with international expertise in managing patients with acromegaly. All participants participated in the workshop proceedings, and the final document written by the scientific committee reflects the consensus opinion of the interactive deliberations. The meeting was supported by an unrestricted educational grant from Ipsen. No pharmaceutical representatives participated in the program planning or in the scientific deliberations.
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Acromegalia/terapia , Acromegalia/tratamento farmacológico , Acromegalia/radioterapia , Acromegalia/cirurgia , Agonistas de Dopamina/uso terapêutico , Feminino , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Somatostatina/análogos & derivados , Somatostatina/uso terapêuticoRESUMO
Monoamine oxidase (MAO) exists in two forms, MAO A and MAO B. Both are present in human brain, but the human platelet contains only MAO B. We studied whether individual variations in the activity of human platelet MAO B reflect individual variations in cerebral cortical MAO activities. Optimal conditions were determined for the measurement of MAO activities in both the platelet and cerebral cortex, obtained from 14 patients with epilepsy during clinically indicated neurosurgery. There was no significant correlation between the activities of MAO B in the cerebral cortex and platelets of these patients. Platelet MAO B activities also failed to correlate significantly with cerebral cortical MAO A activities. However, there was a significant positive correlation between cerebral cortical MAO A and MAO B activities. Individual variations in platelet MAO B activities do not reflect individual variations in either cerebral cortical MAO B or MAO A activities in patients with epilepsy who undergo neurosurgery.
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Plaquetas/enzimologia , Córtex Cerebral/enzimologia , Monoaminoxidase/metabolismo , Adolescente , Adulto , Fatores Etários , Epilepsia/enzimologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Cinética , Masculino , Pessoa de Meia-Idade , Mitocôndrias/enzimologia , Monoaminoxidase/análise , Inibidores da Monoaminoxidase/farmacologia , Selegilina/farmacologiaRESUMO
A clinically, immunohistochemically and ultrastructurally characterized series of 192 pituitary adenomas was analyzed for DNA content by flow cytometry. Results were assessed not only relative to tumor immunotype, size, and invasiveness, but also with frequency of recurrence. Case selection was non-random; males predominated (1.8:1) and the ratio of macro-to-microadenomas was 4.2:1. Female patients were slightly younger and, in all adenoma categories, less often had invasive tumors: PRL (15%/30%), ACTH (17%/44%), LH/FSH (8%/27%) and null cell adenomas (0%/27%). With the exception of prolactin cell adenomas, similar proportions of macroadenomas and invasive tumors in all tumor subtypes were diploid and non-diploid. Prolactin adenomas differed in that tumors of males showed a high rate of non-diploidy (65%); such tumors were predominantly macroadenomas, but only 28% were invasive. Among GH-containing tumors 78% were macroadenomas, 40% were nondiploid, and the frequency of invasive macroadenomas was higher (49%) than in PRL tumors (21%). ACTH adenomas were mainly microadenomas (81%), their rate invasion (29%) and of non-diploidy being low (14%). Among "non-functioning" (LH/FSH, null cell adenomas), LH/FSH-producing tumors were all macroadenomas, but with low rates of invasion (23%) and non-diploidy (9%). Null cell adenomas, nearly all macroadenomas, had similar low invasion rate (21%), but were more often non-diploid (39%). In all adenoma subgroups S-phase fractions were higher in non-diploid adenomas by an overall ratio of 2.1:1. Prolactin adenomas showed the highest (15.2%) and LH/FSH adenomas the lowest (5.6%) mean S-phase fraction. When compared to long-term follow-up, neither this parameter nor ploidy correlated with tumor size or invasiveness. Lastly, long-term follow-up showed ploidy to be an unreliable predictor of tumor persistence or recurrence.
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Adenoma/genética , Adenoma/metabolismo , DNA/metabolismo , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/metabolismo , Ploidias , Adenoma/patologia , Hormônio Adrenocorticotrópico/metabolismo , Feminino , Citometria de Fluxo , Gonadotropinas Hipofisárias/metabolismo , Hormônio do Crescimento Humano/metabolismo , Humanos , Masculino , Invasividade Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasias Hipofisárias/patologia , Fase S , Fatores SexuaisRESUMO
The series involved 11 women with concurrent hyperprolactinemia and primary empty sella syndrome. Eight had amenorrhea and six had galactorrhea. All 11 patients had intact hypothalamic-pituitary function, except for having elevated prolactin levels that ranged from 33 to 498 ng/mL. One patient had primary hypothyroidism. Radiologic investigations included sellar polytomography in eight cases, computed tomography of the head in eight cases, bilateral carotid angiography in six cases, and pneumoencephalography in three cases. Of eight patients undergoing transsphenoidal exploratory surgery, one had a pituitary microadenoma and an empty sella while seven had only an empty sella with a flattened pituitary gland. Conventional histologic methods (seven cases) and immunocytologic studies (three cases) of the pituitary gland showed no abnormalities. The cause of this syndrome is unknown. It should be recognized that hyperprolactinemia, with or without galactorrhea-amenorrhea, may occur in association with an empty sella in the absence of an associated pituitary tumor.
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Síndrome da Sela Vazia/complicações , Doenças da Hipófise/complicações , Neoplasias Hipofisárias/complicações , Prolactina/sangue , Adulto , Idoso , Síndrome da Sela Vazia/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Doenças da Hipófise/diagnóstico por imagem , Testes de Função Hipofisária , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/metabolismo , Tomografia Computadorizada por Raios XAssuntos
Boxe/lesões , Lesões Encefálicas/etiologia , Hematoma Epidural Craniano/etiologia , Hematoma Subdural/etiologia , Futebol/lesões , Adolescente , Adulto , Lesões Encefálicas/diagnóstico por imagem , Hematoma Epidural Craniano/diagnóstico por imagem , Hematoma Subdural/diagnóstico por imagem , Humanos , Masculino , Recuperação de Função Fisiológica , Remissão Espontânea , Tomografia Computadorizada por Raios XRESUMO
We report six cases of meningio-angiomatosis, a disorder of the cerebral cortex of probable malformative origin frequently associated with neurofibromatosis and either asymptomatic or associated with a seizure disorder. The patients, three males and three females, ranged from 10 to 70 years of age at diagnosis. The lesion was an incidental autopsy finding in two patients; four subjects had a seizure disorder which improved following surgical resection of the cortical lesion. In five instances the process was unifocal; one patient with neurofibromatosis had multifocal involvement. Grossly, the lesions were firm, sharply demarcated, transcortical plaques with leptomeningeal calcifications in five cases. The cortical plaques showed characteristic features of meningio-angiomatosis, i.e. a circumscribed, proliferating microvasculature with perivascular meningothelial cell proliferation and fibrosis. In five cases Alzheimer's neurofibrillary change in neurons was present both within the plaques and in the surrounding cortex. Neither senile plaques nor granulovacuolar degeneration were noted. Electron microscopy in one case demonstrated typical intraneuronal accumulations of neurofilaments with regular constrictions. Intracortical vessels lined by endothelial cells with tight junctions were surrounded by pericytes and meningothelial cells. The significance of neurofibrillary tangles described in a variety of disorders, and the factors stimulating their production in the present cases are unknown.