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1.
ESMO Open ; 9(7): 103635, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39043021

RESUMO

BACKGROUND: The number and projections of cancer survivors are necessary to meet the healthcare needs of patients, while data on cure prevalence, that is, the percentage of patients who will not die of cancer by time since diagnosis, are lacking. MATERIALS AND METHODS: Data from Italian cancer registries (duration of registration ranged from 9 to 40 years, with a median of 22 years) covering 47% of the population were used to calculate the limited-duration prevalence, the complete prevalence in 2018, projections to 2030, and cure prevalence, by cancer type, sex, age, and time since diagnosis. RESULTS: A total of 3 347 809 people were alive in Italy in 2018 after a cancer diagnosis, corresponding to 5.6% of the resident population. They will increase by 1.5% per year to 4 012 376 in 2030, corresponding to 6.9% of the resident population, 7.6% of women and ∼22% after age 75 years. In 2030, more than one-half of all prevalent cases (2 million) will have been diagnosed by ≥10 years. Those with breast (1.05 million), prostate (0.56 million), or colorectal cancers (0.47 million) will be 52% of all prevalent patients. Cure prevalence was 86% for all patients alive in 2018 (87% for patients with breast cancer and 99% for patients with thyroid or testicular cancer), increasing with time since diagnosis to 93% for patients alive after 5 years and 96% after 10 years. Among patients who survived at least 5 years, the excess risk of death (1 - cure prevalence) was <5% for patients with most cancer types except for those with cancers of the breast (8.3%), lung (11.1%), kidney (13.2%), and bladder (15.5%). CONCLUSIONS: Study findings encourage the implementation of evidence-based policies aimed at improving long-term clinical follow-up and rehabilitation of people living after cancer diagnosis throughout the course of the disease. Updated estimates of complete prevalence are important to enhance data-driven cancer control planning.

2.
Br J Cancer ; 111(5): 987-97, 2014 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-24937665

RESUMO

BACKGROUND: Three prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC use is a protective factor for EC risk. METHODS: Cox regression was used to estimate hazard ratios (HRs) for the association between acrylamide intake and EC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU acrylamide monitoring database, which was matched with EPIC questionnaire-based food consumption data. Acrylamide intake was energy adjusted using the residual method. RESULTS: No associations were observed between acrylamide intake and overall EC (n=1382) or type-I EC risk (n=627). We observed increasing relative risks for type-I EC with increasing acrylamide intake among women who both never smoked and were non-users of OCs (HRQ5vsQ1: 1.97, 95% CI: 1.08-3.62; likelihood ratio test (LRT) P-value: 0.01, n=203). CONCLUSIONS: Dietary intake of acrylamide was not associated with overall or type-I EC risk; however, positive associations with type I were observed in women who were both non-users of OCs and never smokers.


Assuntos
Acrilamida/efeitos adversos , Ingestão de Alimentos/fisiologia , Neoplasias do Endométrio/etiologia , Estudos de Coortes , Dieta/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Estado Nutricional/fisiologia , Estudos Prospectivos , Risco , Fatores de Risco , Fumar/efeitos adversos
3.
J Thromb Haemost ; 11(2): 315-24, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23256818

RESUMO

BACKGROUND: Severe clotting deficiencies are associated with enhanced in vitro fibrinolysis due to insufficient thrombin activatable fibrinolysis inhibitor (TAFI) activation. Because oral anticoagulant therapy (OAT) with warfarin causes a partial deficiency of vitamin K-dependent factors, its effect on clot lysability remains unclear. OBJECTIVES: To evaluate plasma and blood fibrinolytic capacity in patients under stable OAT (n = 221) as compared with controls (n = 132). METHODS: Fibrinolysis resistance of plasma (turbidimetry) and blood (thromboelastography) clots was calculated as the lysis time of tissue factor-induced clots exposed to 30 and 100 ng mL(-1) t-PA, respectively. RESULTS: Plasma PAI-1 was similar in the two groups, whereas TAFI was slightly lower in patients. OAT plasma clots lysed faster than controls (P = 0.001). The addition of the TAFIa inhibitor PTCI reduced lysis time by 14% in OAT and 34% in controls, and the difference between the groups disappeared. Similar data were obtained with blood clots. Thrombin and TAFIa generation in OAT plasma amounted to roughly 50% of controls, supporting a reduced thrombin-dependent TAFI activation. Clot resistance of OAT plasma was normalized by Ba-citrate plasma eluate or prothrombin but not by BaSO(4) serum eluate, rFVIIa or FX. Surprisingly, circulating levels of TAFIa and its inactive derivative TAFIai were higher in warfarin patients (P < 0.0001) and correlated with plasmin-antiplasmin (P = 0.0001) but not with prothrombin F(1) (+) (2) . CONCLUSIONS: OAT enhances both plasma and blood fibrinolysis by reducing thrombin-dependent TAFI activation, a phenomenon largely determined by low prothrombin levels. At variance with in vitro data, 'basal' in vivo TAFIa/ai levels seem related to plasmin rather than thrombin generation.


Assuntos
Anticoagulantes/administração & dosagem , Carboxipeptidase B2/sangue , Fibrinólise/efeitos dos fármacos , Trombina/metabolismo , Varfarina/administração & dosagem , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Tempo de Lise do Coágulo de Fibrina , Fibrinolisina/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Nefelometria e Turbidimetria , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Protrombina , Tromboelastografia , alfa 2-Antiplasmina/metabolismo
4.
Neuroradiol J ; 25(4): 475-80, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24029040

RESUMO

Paget's disease (PD) is a common focal progressive osteometabolic disorder characterised by a disturbance in bone modelling and remodelling, because of an increase in osteoblastic and osteoclastic activity. It is a condition of unknown aetiology affecting approximately 3% of the population over 40 years of age and, approximately 10% of those over the age of 85 years. It is most common in Northern Europe and Australia and is rare in Asia and Africa. We describe the case of a 71-year-old man diagnosed with PD confined to the sacrum. After laboratory test, an imaging study with radiography, scintigraphy, computed tomography (CT) and magnetic resonance imaging (MRI) was performed disclosing findings compatible with Paget's disease in middle pathologic phase. The diagnosis was confirmed at biopsy. The structural modification of the sacrum with spongiosa rarefaction, thickening of bone and intact bone cortical, confirmed by CT, are tipical of an intermediate phase of PD. This was also supported by signal MRI changes showing substitution of the red by the fat medulla, visualized by FS sequences. Once the treatment for the bone disease was established, the patient no longer complained of pain. Special attention should be paid to male and elderly patients with pain in the lumbar spine because of the potential risk cancer development (21). The radiologist must be attentive to the possible presentations and complications of PD, even in uncommon sites, trying whenever possible to correlate the radiological features with the patient's clinical symptoms.

5.
Br J Cancer ; 105(9): 1436-42, 2011 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-21915124

RESUMO

BACKGROUND: It is well established that parity and use of oral contraceptives reduce the risk of ovarian cancer, but the associations with other reproductive variables are less clear. METHODS: We examined the associations of oral contraceptive use and reproductive factors with ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 327,396 eligible women, 878 developed ovarian cancer over an average of 9 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models stratified by centre and age, and adjusted for smoking status, body mass index, unilateral ovariectomy, simple hysterectomy, menopausal hormone therapy, and mutually adjusted for age at menarche, age at menopause, number of full-term pregnancies and duration of oral contraceptive use. RESULTS: Women who used oral contraceptives for 10 or more years had a significant 45% (HR, 0.55; 95% CI, 0.41-0.75) lower risk compared with users of 1 year or less (P-trend, <0.01). Compared with nulliparous women, parous women had a 29% (HR, 0.71; 95% CI, 0.59-0.87) lower risk, with an 8% reduction in risk for each additional pregnancy. A high age at menopause was associated with a higher risk of ovarian cancer (>52 vs ≤ 45 years: HR, 1.46; 95% CI, 1.06-1.99; P-trend, 0.02). Age at menarche, age at first full-term pregnancy, incomplete pregnancies and breastfeeding were not associated with risk. CONCLUSION: This study shows a strong protective association of oral contraceptives and parity with ovarian cancer risk, a higher risk with a late age at menopause, and no association with other reproductive factors.


Assuntos
Anticoncepcionais Orais/administração & dosagem , Neoplasias Ovarianas/epidemiologia , História Reprodutiva , Adulto , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Paridade , Gravidez , Risco
6.
J Thromb Haemost ; 9(1): 154-62, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20961395

RESUMO

BACKGROUND: The resistance of platelet-rich thrombi to fibrinolysis is generally attributed to clot retraction and platelet PAI-1 release. The role of TAFI in platelet-mediated resistance to lysis is unclear. OBJECTIVE: We investigated the contribution of TAFI to the antifibrinolytic effect of platelets in whole blood by thromboelastography. METHODS: Platelet-poor (PP-WB, < 40 × 10(3) µL(-1) ) and platelet-rich (PR-WB, > 400 × 10(3) µL(-1) ) blood samples were obtained from normal human blood (N-WB, 150-220 × 10(3) µL(-1) ). Clot lysis time was measured by thromboelastography in recalcified blood supplemented with t-PA (100 ng mL(-1) ) and tissue factor (1:1000 Recombiplastin). RESULTS: t-PA-induced lysis time increased in parallel with platelet concentration (up to 3-fold). Neutralization of TAFI, but not of PAI-1, shortened the lysis time by ∼ 50% in PR-WB and by < 10% in PP-WB. Accordingly, prothrombin F1+2 and TAFIa accumulation was greater in PR-WB than in PP-WB. A similar TAFI-dependent inhibition of fibrinolysis was observed when clot retraction was prevented by cytochalasin D or abciximab, or when platelet membranes were tested. Moreover, in blood with an intact contact system, platelet-mediated fibrinolysis resistance was attenuated by an anti-FXI but not by an anti F-XII antibody. Finally, platelets made the clots resistant to the profibrinolytic effect of heparin concentrations displaying a strong anticoagulant activity. CONCLUSIONS: Our data indicate that TAFI activation is one major mechanism whereby platelets make clots resistant to fibrinolysis and underscore the importance of TAFI inhibitors as new antithrombotic agents.


Assuntos
Plaquetas/metabolismo , Carboxipeptidase B2/sangue , Fator XI/metabolismo , Fibrinólise , Tromboelastografia , Abciximab , Anticorpos Monoclonais/farmacologia , Anticoagulantes/farmacologia , Plaquetas/efeitos dos fármacos , Citocalasina D/farmacologia , Fibrinólise/efeitos dos fármacos , Heparina/farmacologia , Humanos , Fragmentos Fab das Imunoglobulinas/farmacologia , Fragmentos de Peptídeos/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Inibidores da Agregação Plaquetária/farmacologia , Protrombina , Tromboplastina/metabolismo , Fatores de Tempo , Ativador de Plasminogênio Tecidual/sangue
7.
Diabetologia ; 53(10): 2167-76, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20523966

RESUMO

AIMS/HYPOTHESIS: We sought to establish the extent and basis for adaptive changes in beta cell numbers in human pregnancy. METHODS: Pancreas was obtained at autopsy from women who had died while pregnant (n = 18), post-partum (n = 6) or were not pregnant at or shortly before death (controls; n = 20). Pancreases were evaluated for fractional pancreatic beta cell area, islet size and islet fraction of beta cells, beta cell replication (Ki67) and apoptosis (TUNEL), and indirect markers of beta cell neogenesis (insulin-positive cells in ducts and scattered beta cells in pancreas). RESULTS: The pancreatic fractional beta cell area was increased by approximately 1.4-fold in human pregnancy, with no change in mean beta cell size. In pregnancy there were more small islets rather than an increase in islet size or beta cells per islet. No increase in beta cell replication or change in beta cell apoptosis was detected, but duct cells positive for insulin and scattered beta cells were increased with pregnancy. CONCLUSIONS/INTERPRETATION: The adaptive increase in beta cell numbers in human pregnancy is not as great as in most reports in rodents. This increase in humans is achieved by increased numbers of beta cells in apparently new small islets, rather than duplication of beta cells in existing islets, which is characteristic of pregnancy in rodents.


Assuntos
Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Adolescente , Adulto , Apoptose , Contagem de Células , Proliferação de Células , Tamanho Celular , Feminino , Humanos , Imuno-Histoquímica , Gravidez
8.
Cent Nerv Syst Agents Med Chem ; 10(2): 91-6, 2010 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-20518725

RESUMO

Genetic factors that increase susceptibility to oxidative stress, endothelial disfunction and, possibly, stroke include angiotensin-converting enzyme gene deletion polymorphism (ACE-DD) and the methylentetrahydropholate reductase (MTHFR) C677-TT polymorphism. The relationship of ACE-DD genotype to ischemic stroke and cardiovascular disease is controversial, but it has been independently linked to lacunar infarction, in the absence of carotid atheroma. Lea et al. (2005) reported that the ACE DD genotype acts in combination with the MTHFR T/T genotype to increase migraine susceptibility, with the greatest effect in those with aura. The "TT" polymorphism is also associated with an increased risk of migraine with aura, independent of other cardiovascular risk factors. The aim of our study was to evaluate the incidence of ACE and MTHFR genes polymorphisms in a consecutive series of migrainous patients and of patients affected by myocardial infarction. We studied a series of 103 migrainous patients (1), whose age was between 13 and 75 years (81 suffering from migraine without aura, MwA, 9 from migraine with aura, MWA, 13 from mixed forms MwA-MWA, according to ICHD-II 2004 criteria) and of 336 patients (2) suffering from ischaemic cardiopathy (myocardial infarction, MI). The analysis, based on Polymerase Chain Reaction (PCR) and on reverse-hybridization, showed as follows: MTHFR (C677T): 60 patients (58%) (1) and 186 (56%) (2) were heterozygous; 9 patients (9%) (1) and 54 (16%) (2) were mutated. The result of 1 patient (2) was unknown. MTHFR (A1298C): 54 patients (52%) (1) and 146 (44%) (2) were heterozygous, 7 patients (7%) (1) and 33 (10%) (2) were mutated. The result of 1 patient (2) was unknown. ACE (evaluated on 101 patients (1) and 245 (2)): 45 patients (43%) (1) and 133 (54%) (2) had an ID genotype; 42 (41%) (1) and 87 (36%) (2) had a DD genotype. The results of our study confirm the high incidence in the genetic polymorphisms ACE and MTHFR in migraineuse. These data are confirmed in the sample of patients affected by myocardial infarction. This gives evidence of a strong relationship between migraine and major vascular diseases and let us hypothesize an important role of ACE and MTHFR system in the pathogenetic model of migraine for its capability to interfere with the endothelial regulation tone. Once an effective role in the genesis of migraine and in the increased risk of migrainous patients to evolve into an ischemic pathology has been obviously assigned to this genetic mutation, future researches must aim through wider and more controlled casistics also to clarify the role that drugs acting on these systems may have on the resolution of these diseases.


Assuntos
Doença da Artéria Coronariana/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Transtornos de Enxaqueca/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Adolescente , Adulto , Idoso , Doença da Artéria Coronariana/enzimologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/enzimologia , Adulto Jovem
9.
Diabetologia ; 53(1): 111-4, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19847395

RESUMO

AIMS/HYPOTHESIS: We sought to establish the relationship between fasting plasma glucose concentrations and pancreatic fractional beta cell area in adult cynomolgus monkeys (Macaca fascicularis). METHODS: Fasting plasma glucose and pancreatic fractional beta cell area were measured in 18 control and 17 streptozotocin-treated adult primates (17.0 +/- 1.2 vs 15.4 +/- 1.2 years old). RESULTS: Fasting plasma glucose was increased (12.0 +/- 2.0 vs 3.4 +/- 0.1 mmol/l, p < 0.01) and fractional beta cell area was decreased (0.62 +/- 0.13% vs 2.49 +/- 0.35%, p < 0.01) in streptozotocin-treated monkeys. The relationship between fasting plasma glucose and pancreatic fractional beta cell area was described by a wide range of beta cell areas in controls. In streptozotocin-treated monkeys there was an inflection of fasting blood glucose at approximately 50% of the mean beta cell area in controls with a steep increase in blood glucose for each further decrement in beta cell area. CONCLUSIONS/INTERPRETATION: In adult non-human primates a decrement in fractional beta cell area of approximately 50% or more leads to loss of glycaemic control.


Assuntos
Glicemia/metabolismo , Hiperglicemia/sangue , Células Secretoras de Insulina/patologia , Animais , Diabetes Mellitus Experimental/patologia , Jejum , Humanos , Hiperglicemia/patologia , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/fisiologia , Macaca fascicularis , Masculino
10.
Diabetologia ; 53(1): 21-6, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19844672

RESUMO

AIMS/HYPOTHESIS: In a high-fat-fed rat model of type 2 diabetes we noted increased exocrine duct replication. This is a predisposing factor for pancreatitis and pancreatic cancer, both of which are more common in type 2 diabetes. The aim of the study reported here was to establish if obesity and/or type 2 diabetes are associated with increased pancreatic ductal replication in humans. METHODS: We obtained pancreas at autopsy from 45 humans, divided into four groups: lean (BMI <25 kg/m(2)); obese (BMI >27 kg/m(2)); non-diabetic; and with type 2 diabetes. Pancreases were evaluated after immunostaining for the duct cell marker cytokeratin and Ki67 for replication. RESULTS: We show for the first time that both obesity and type 2 diabetes in humans are associated with increased pancreatic ductal replication. Specifically, we report that (1) replication of pancreatic duct cells is increased tenfold by obesity, and (2) lean subjects with type 2 diabetes demonstrate a fourfold increase in replication of pancreatic duct cells compared with their lean non-diabetic controls. CONCLUSIONS/INTERPRETATION: Pancreatic duct cell replication is increased in humans in response to both obesity and type 2 diabetes, potentially providing a mechanism for the increased risk of pancreatitis and pancreatic cancer in those with obesity and/or type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/patologia , Obesidade/patologia , Ductos Pancreáticos/patologia , Idoso , Idoso de 80 Anos ou mais , Animais , Autopsia , Índice de Massa Corporal , Divisão Celular , Diabetes Mellitus Tipo 2/fisiopatologia , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Ductos Pancreáticos/fisiopatologia , Ratos
11.
Neuroradiology ; 51(7): 471-6, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19300988

RESUMO

INTRODUCTION: This study aimed to illustrate the validity of the treatment with vertebroplasty (VP) in patients with aggressive or symptomatic vertebral hemangioma (VH) with or without epidural extension. METHODS: From January 2003 to December 2007, 24 consecutive patients have been treated with VP, for a total of 36 vertebral bodies affected by VH: two cervical, ten dorsal, 24 lumbar. All the patients complained of a pain syndrome resistant to continuous medical medication; four of 24 patients also presented aggressive magnetic resonance features of the vertebral lesion and two patients showed also epidural extension. A unipedicular approach has been performed in 16 patients; a bipedicular approach has been performed in six, while for the cervical spine an anterior-lateral approach with manual dislocation of the carotid axis has always been performed. Bone biopsy was never done. All procedures have been carried out with local anesthesia, except for the treatment of the cervical hemangiomas which has always been performed under general anesthesia. Four vertebral bodies in the same session have been treated in one case. RESULTS: Results have been evaluated with the visual analog scale and the Oswestry Disability Index methods. In all the patients, in the following 24-72 h, a successful outcome has been observed with a complete resolution of pain symptom. Extravertebral vascular or discal cement leakage has been observed in four patients, without any onset of clinical radicular syndrome due to epidural diffusion. Clinical and radiological follow-up until 4 years has been performed in 12 patients and it showed stability of the treatment and absence of pain. CONCLUSIONS: Percutaneous treatment with VP for aggressive and symptomatic vertebral hemangiomas even with epidural extension is a valuable, mini-invasive, and quick method that allows a complete and enduring resolution of the painful vertebral symptoms without findings of fracture of a vertebral body adjacent or distant to the one treated.


Assuntos
Hemangioma/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Vertebroplastia/métodos , Avaliação da Deficiência , Epiderme/patologia , Feminino , Seguimentos , Hemangioma/complicações , Hemangioma/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Dor/etiologia , Dor/cirurgia , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/patologia , Coluna Vertebral/patologia , Coluna Vertebral/cirurgia , Resultado do Tratamento
12.
Neuroradiol J ; 22(1): 108-21, 2009 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-24206960

RESUMO

Low back pain is the commonest spine disease causing absence from work in developed countries. Low back pain with classical irradiation along the course of the nerve root affected is more frequently due to disc disease. In 60-80% of patients with herniated disc, radicular symptoms disappear with conservative treatment after about six weeks, the remainder are treated surgically with a 2-6% of incidence of true recurrence of herniation post-intervention and with failed back surgery syndrome in 15% of cases. Recently minimally invasive techniques have developed as "alternative" treatments to surgical intervention. This review aimed to assess the pathogenesis of low back pain caused by lumbar disc hernia as a basis for action of minimally invasive techniques; to illustrate the techniques already used or currently in use, to compare them in technical guidance, indications and complications, exposing for each of them the inclusion/exclusion criteria in enrolling patients and the imaging guide technique of choice. Minimally invasive techniques can be a valuable alternative to traditional surgery with low cost, low risk of complications, easy feasibility, and in the event of failure they do not exclude subsequent surgery.

13.
Interv Neuroradiol ; 15(2): 153-7, 2009 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-20465892

RESUMO

SUMMARY: This study illustrates the usefulness of vertebral biopsy in osteoporotic patients previously treated with vertebroplasty (VP) who present at follow-up with a new fracture in a vertebral soma adjacent or distant from the collapsed vertebral body. Five hundred and fifty patients with osteoporotic vertebral collapse underwent a minimally invasive treatment with vertebroplasty (VP) for a total of 980 vertebral bodies. The approach was unipedicular in 520 patients and bipedicular in 30. Only cases with unclear findings at MR or CT (23 patients) were scheduled for a vertebral biopsy before VP treatment. The biopsy results were positive for haematological disease in only eight patients. A vertebral biopsy was carried out during re-treatment with VP in all patients who presented a vertebral refracture in the three month follow-up at a site adjacent to or distant from the previously treated vertebra (21 patients). We have found new fractures of adjacent vertebrae in 15 patients and new fractures of distant vertebrae in 16 patients at three month follow-up examination. Five of the 31 cases (16%) of spinal refracture, where during vertebroplasty treatment a bone biopsy and a sternal medullary aspiration had been carried out, an anatomopathological response to multiple myeloma was responsible for the refracture. It is useful to perform a spinal bone biopsy during re-treatment of the vertebroplasty procedure to rule out multiple myeloma or other disease as the cause of the new collapse in patients with osteoporotic disease presenting a new vertebral fracture in an adjacent or distant site from the previously collapsed vertebral body.

14.
Nutr Metab Cardiovasc Dis ; 18(10): 659-63, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18450435

RESUMO

BACKGROUND AND AIMS: Clinical studies suggest that menstrual irregularities are associated with metabolic and hormonal abnormalities, insulin resistance and a hyperestrogenic/hyperandrogenic imbalance, that may influence the risk of cardiovascular disease. METHODS AND RESULTS: The association of these abnormalities with the metabolic syndrome suggests that information on lipid patterns at different menstrual cycle length may be of interest in identifying women at higher cardiovascular risk. The association of lipid patterns with menstrual cycle length was evaluated in a cohort of 5062 women participating in the Progetto ATENA Study. Questions were administered to the participants about their cycle lengths at different periods of time over their reproductive life. The period between 20 and 50 years was investigated: normal cycle length was defined as short (30 days). Perimenopausal women were excluded and variables adjusted for age, BMI and menopausal status. In 4434 participants serum triglycerides were found to increase with an increased number of days in the menstrual cycle: 106 mg/dl in the short cycle pattern (21-26 days); 113 mg/dl in the medium cycle pattern (27-29 days); and 116 mg/dl in the long cycle pattern (30-31 days), whereas total and LDL cholesterol were found to be higher and HDL was lower in women with longer cycles, but the difference was not statistically significant. The results were very similar when the same adjusted analysis was restricted to a subgroup of 3823 women with a stable cycle length over the fourth and the fifth decade of life. CONCLUSIONS: These results suggest that cycle length may be a marker of higher cardiovascular risk due to associated metabolic and hormonal patterns.


Assuntos
Lipídeos/sangue , Lipoproteínas/sangue , Ciclo Menstrual , Adulto , Idoso , Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Triglicerídeos/sangue
15.
Diabetologia ; 50(11): 2323-31, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17805509

RESUMO

AIMS/HYPOTHESIS: Type 1 diabetes is characterised by a deficit in beta cell mass thought to be due to immune-mediated increased beta cell apoptosis. Beta cell turnover has not been examined in the context of new-onset type 1 diabetes with diabetic ketoacidosis. METHODS: Samples of pancreas were obtained at autopsy from nine patients, aged 12 to 38 years (mean 24.3+/-3.4 years), who had had type 1 diabetes for less than 3 years before death due to diabetic ketoacidosis. Samples of pancreas obtained at autopsy from nine non-diabetic cases aged 11.5 to 38 years (mean 24.2+/-3.4 years) were used as control. Fractional beta cell area (insulin staining), beta cell replication (insulin and Ki67 staining) and beta cell apoptosis (insulin and TUNEL staining) were measured. RESULTS: In pancreas obtained at autopsy from recent-onset type 1 diabetes patients who had died of diabetic ketoacidosis, the beta cell deficit varied from 70 to 99% (mean 90%). The pattern of beta cell loss was lobular, with almost all beta cells absent in most pancreatic lobules; islets in lobules not devoid of beta cells had reduced or a near-normal complement of beta cells. Beta cell apoptosis was increased in recent-onset type 1 diabetes, but to a surprisingly modest degree given the marked hyperglycaemia (30 mmol/l), acidosis and presumably high NEFA. Beta cell replication, scattered pancreatic beta cells and beta cells in exocrine ducts were not increased in recent-onset type 1 diabetes. CONCLUSIONS/INTERPRETATION: These findings do not support the notion of active beta cell regeneration by replication in new-onset type 1 diabetes under conditions of diabetic ketoacidosis. The gluco-lipotoxicity reported in isolated human islets may be less evident in vivo.


Assuntos
Diabetes Mellitus Tipo 1/mortalidade , Cetoacidose Diabética/mortalidade , Células Secretoras de Insulina/patologia , Adolescente , Adulto , Apoptose , Autopsia , Divisão Celular , Criança , Feminino , Humanos , Insulina/análise , Masculino , Pâncreas/patologia , Valores de Referência
16.
Diabetologia ; 49(11): 2689-96, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17016695

RESUMO

AIMS/HYPOTHESIS: Type 1 and type 2 diabetes are characterised by a beta cell deficit. Islet hyperplasia has been described in patients with Zollinger-Ellison syndrome secondary to gastrin-producing tumours (gastrinomas), and gastrin therapy has increased beta cell mass in rodents and human islets in vitro. In the present studies we addressed the following questions: (1) In pancreas specimens from gastrinoma cases, is the fractional beta cell area increased? (2) If so, is this restricted to tumour-adjacent islets or also present in tumour-distant islets? (3) Is new beta cell formation (beta cell replication and islet neogenesis) increased and beta cell apoptosis decreased in pancreas specimens from gastrinoma cases? METHODS: Pancreas was obtained at surgery from four patients with Zollinger-Ellison syndrome caused by pancreatic gastrinomas and 15 control subjects at autopsy. RESULTS: Islet fractional beta cell area (p<0.001), islet size (p<0.001) and beta cell replication (Ki67 staining) (p<0.05) were increased in islets adjacent to the tumours, but not in tumour-distant pancreas, compared with control subjects. We did not observe any differences in beta cell apoptosis or in the number of insulin-positive cells in ducts either adjacent to or distant from the tumour. CONCLUSIONS/INTERPRETATION: One or more factors released by human gastrinomas increase beta cell replication in islets immediately adjacent to the tumour, but not in tumour-distant islets. While these findings demonstrate that adult human beta cells can be driven into the cell cycle, they caution against the therapeutic usefulness of gastrin, since islets located >1 cm away from the gastrinomas did not exhibit changes in beta cell turnover, despite markedly elevated systemic gastrin levels sufficient to cause severe gastrointestinal symptoms.


Assuntos
Divisão Celular/fisiologia , Gastrinoma/patologia , Células Secretoras de Insulina/patologia , Neoplasias Pancreáticas/patologia , Índice de Massa Corporal , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/patologia , Gastrinoma/cirurgia , Gastrinas/sangue , Humanos , Células Secretoras de Insulina/fisiologia , Ilhotas Pancreáticas/patologia , Pessoa de Meia-Idade , Neoplasias Pancreáticas/cirurgia , Síndrome de Zollinger-Ellison/patologia , Síndrome de Zollinger-Ellison/cirurgia
17.
Diabetologia ; 49(8): 1838-44, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16802132

RESUMO

AIMS/HYPOTHESIS: We investigated whether there was evidence of attempted beta cell regeneration in the pancreas obtained from a patient with recent-onset type 1 diabetes, and if so by what mechanism this occurred. SUBJECTS, MATERIALS AND METHODS: We examined pancreas tissue from a lean 89-year-old patient (BMI 18.0 kg/m(2)) with recent-onset type 1 diabetes who had had a distal pancreatectomy to remove a low-grade pancreatic intraepithelial neoplasia. RESULTS: In the tumour-free tissue, the fractional beta cell area was 0.54+/-0.2% of pancreas area (about one-third of that in non-diabetic humans). CD3-positive T lymphocytes and macrophages had infiltrated the majority of the islets. Subclassification of the T cell population revealed a predominance of CD8-positive cells over CD4-positive cells. Beta cell apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling [TUNEL] staining) was greatly increased, consistent with ongoing immune-mediated beta cell destruction. There was also a marked increase (more than approximately 100-fold) in the frequency of beta cell replication (0.69+/-0.15% Ki67-positive beta cells) in all blocks examined. CONCLUSIONS/INTERPRETATION: The present report provides direct evidence of attempted beta cell regeneration through the mechanism of beta cell replication in a case of newly diagnosed type 1 diabetes, and affirms that beta cell apoptosis is an important mechanism for beta cell loss in type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Ilhotas Pancreáticas/fisiopatologia , Idade de Início , Idoso de 80 Anos ou mais , Humanos , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Masculino , Pancreatectomia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Regeneração
18.
Eur J Clin Nutr ; 60(10): 1168-73, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16685284

RESUMO

BACKGROUND: Nutrient determinants of postprandial triglyceride (TG) are matter of debate, especially for type II diabetes. OBJECTIVE: This study was performed to evaluate the impact of dietary habits on postprandial TG response in a population-based sample of type II diabetic patients. DESIGN: One-hundred and forty type II diabetic patients (63 men/77 women, age 45-70 years) referring to the same health district, not on hypolipidemic drugs and without any other chronic disease, performed four TG profiles (at fasting, before, 2 and 3 h after lunch) with a specific device (Accutrend GCT, Roche Diagnostics Mannheim, Germany) validated previously. Dietary habits were recorded by a dietitian utilizing a previously validated semiquantitative questionnaire. RESULTS: Triglyceride values (mmol/l, mean +/- s.d.) were 2.22 +/- 0.93 at fasting, decreased before lunch (2.03 +/- 0.81), reached peak values 3 h after lunch (2.73 +/- 1.11). Postprandial TG increments (3 h after lunch minus pre-lunch concentration) significantly correlated with the intake (g/day) of animal protein (r = 0.20, P < 0.02), total fat (r = 0.21, P < 0.01), animal fat (r = 0.19, P < 0.03) and vegetable fat (r = 0.19, P < 0.03), also after adjusting for fasting TG and high-density lipoprotein cholesterol levels. Expressing nutrient intake as percentage of total calorie intake, total and animal fat remained significantly and directly related to postprandial TG increment (r = 0.21, P < 0.01 for total fat; r = 0.19, P < 0.03 for animal fat) whereas the percentage of carbohydrates was inversely related (r = -0.23, P < 0.007). CONCLUSIONS: Fat intake seems the major nutritional determinant of postprandial TG response in type II diabetic patients.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Gorduras na Dieta/farmacocinética , Período Pós-Prandial , Triglicerídeos/sangue , Idoso , Área Sob a Curva , Glicemia/metabolismo , Doenças Cardiovasculares/epidemiologia , Colesterol/sangue , Gorduras na Dieta/metabolismo , Jejum/sangue , Comportamento Alimentar , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários
19.
Eur J Clin Nutr ; 59(12): 1387-96, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16160702

RESUMO

OBJECTIVE: The aim in this study was to assess the association between individual plasma carotenoid levels (alpha-carotene, beta-carotene, lycopene, beta-cryptoxanthin, lutein, zeaxanthin) and fruit and vegetable intakes recorded by a calibrated food questionnaire (FQ) and 24-h dietary recall records (24HDR) in nine different European countries with diverse populations and widely varying intakes of plant foods. DESIGN: A stratified random subsample of 3089 men and women from nine countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), who had provided blood samples and dietary and other lifestyle information between 1992 and 2000, were included. RESULTS: beta-Cryptoxanthin was most strongly correlated with total fruits (FQ r = 0.52, 24HDR r = 0.39), lycopene with tomato and tomato products (FQ r = 0.38, 24HDR r = 0.25), and alpha-carotene with intake of root vegetables (r = 0.39) and of total carrots (r = 0.38) for FQ only. Based on diet measured by FQ and adjusting for possible confounding by body mass index (BMI), age, gender, smoking status, alcohol intake, and energy intake, the strongest predictors of individual plasma carotenoid levels were fruits (R(partial)(2) = 17.2%) for beta-cryptoxanthin, total carrots ((partial)(2) = 13.4%) and root vegetables (R(partial)(2) = 13.3%) for alpha-carotene, and tomato products (R(partial)(2) = 13.8%) for lycopene. For 24HDR, the highest R(partial)(2) was for fruits in relation to beta-cryptoxanthin (7.9%). CONCLUSIONS: Intakes of specific fruits and vegetables as measured by food questionnaires are good predictors of certain individual plasma carotenoid levels in our multicentre European study. At individual subject levels, FQ measurements of fruits, root vegetables and carrots, and tomato products are, respectively, good predictors of beta-cryptoxanthin, alpha-carotene, and lycopene in plasma.


Assuntos
Antioxidantes/metabolismo , Carotenoides/sangue , Frutas , Verduras , Consumo de Bebidas Alcoólicas , Biomarcadores/sangue , Índice de Massa Corporal , Estudos de Coortes , Estudos Transversais , Criptoxantinas , Feminino , Humanos , Estilo de Vida , Luteína/sangue , Masculino , Rememoração Mental , Pessoa de Meia-Idade , Estudos Prospectivos , Estações do Ano , Fumar , Inquéritos e Questionários , Xantofilas , Zeaxantinas , beta Caroteno/análogos & derivados , beta Caroteno/sangue
20.
Bone Marrow Transplant ; 31(7): 525-30, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12692616

RESUMO

Data from eight randomised trials on high-dose chemotherapy (HDC) for metastatic breast cancer (MBC) have been published, but only seven studies are evaluable after the Bezwoda trial was discredited. Moreover, overall survival (OS) has been evaluated in only four out of seven studies since three had a crossover design. OS was similar for the HDC and standard-dose chemotherapy (SDC) group in the four evaluable trials, while disease-free survival (DFS) was improved in the HDC group in six of the seven trials. The delay in relapse for patients with metastatic disease represents an important clinical outcome; furthermore, since none of the reported studies randomised more than 220 patients, their statistical power may have been too limited to detect meaningful survival differences. Finally, preliminary experiences have shown that HDC seems to be the ideal platform upon which to build novel therapies. In conclusion, HDC remains an important field of clinical research for breast cancer patients with stage IV disease and, from the studies reported in this article, there is some evidence for offering this therapeutic modality to selected patients who are interested in a medically aggressive approach.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/secundário , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
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