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INTRODUCTION: Body integrity dysphoria (BID) is a rare condition in which individuals experience a long-lasting desire to achieve a specific physical disability. In this study, we tested the hypothesis of interoceptive and affective abnormalities in BID, in line with the evidence of structural and functional alteration of the interoceptive-affective neural system in these individuals. METHOD: Our study involved 68 participants with BID (mean age: 35.6, SD: 16.4). Among these participants, 47 expressed a desire for amputation, 14 desired paralysis, 3 sought sensory deprivation, and 3 desired a combination of these forms. For comparisons, we recruited a control group of 79 participants (mean age: 35.2, SD: 15.8). We administered assessment measures to investigate alexithymia level (TAS-20), disgust sensitivity (DS-R), interoceptive awareness (MAIA-2), and (affective and cognitive) empathy (QCAE). We also administered the Short Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE) to identify psychiatric comorbidities. Subgroups with low O-LIFE scores (BID = 31; controls = 43) and subgroups with high O-LIFE scores (BID = 37; controls = 36) were derived through a median-split procedure. RESULTS: Within the BID low O-LIFE group, we found reduced interoceptive sensibility, reduced disgust sensitivity, and increased difficulty in identifying feelings, which refers to a dimension of the alexithymia trait. Within the BID high O-LIFE group, we observed a reduced disgust sensitivity and interoceptive sensibility, accompanied by a diminished score in cognitive empathy. CONCLUSION: Our study suggests that BID can be associated with altered interoceptive and affective processing.
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Emoções , Interocepção , Humanos , Adulto , Sintomas Afetivos/psicologia , Autorrelato , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are considered as a homogeneous cohort of patients. However, the specific role of diabetic microvascular complications (DMC), in determining the features of coronary plaques is poorly known. We investigated whether the presence of DMC may identify a different phenotype of patients associated to specific clinical, angiographic, optical coherence tomography (OCT) features and different prognosis. METHODS: We prospectively enrolled consecutive T2DM patients with obstructive coronary artery disease (CAD) at their first coronary event. Patients were stratified according to the presence or absence of DMC, including diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. OCT assessment of the culprit vessel was performed in a subgroup of patients. The incidence of major adverse cardiac events (MACEs) was assessed at follow-up. RESULTS: We enrolled 320 T2DM patients (mean age 70.3 ± 8.8 years; 234 [73.1%] men, 40% acute coronary syndrome, 60% chronic coronary syndrome). Patients with DMC (172 [53.75%]) presented a different clinical and biochemical profile and, of importance, a higher prevalence of multivessel CAD (109 [63.4%] vs. 68 [45.9%], p = 0.002). At OCT analysis, DMC was associated to a higher prevalence of large calcifications and healed plaques and to a lower prevalence of lipid plaques. Finally, MACEs rate was significantly higher (25 [14.5%] vs. 12 [8.1%], p = 0.007) in DMC patients, mainly driven by a higher rate of planned revascularizations, and DMC predicted the occurrence of MACEs (mean follow-up 33.4 ± 15.6 months). CONCLUSIONS: The presence of DMC identifies a distinct diabetic population with more severe CAD but with a more stable pattern of coronary atherosclerosis.
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Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Placa Aterosclerótica , Angiografia Coronária/métodos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Vasos Coronários/diagnóstico por imagem , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Lipídeos , Fenótipo , Placa Aterosclerótica/complicações , Prognóstico , Fatores de Risco , Tomografia de Coerência Óptica/métodosRESUMO
BACKGROUND AND AIMS: Diabetes mellitus (DM) is a risk factor for left ventricle (LV) diastolic dysfunction. Aim of this study was to investigate whether endothelial and/or autonomic dysfunction are associated with LV diastolic dysfunction in DM patients. METHODS: We studied 84 non-insulin-dependent type 2 DM (T2DM) patients with no heart disease by assessing: 1) LV diastolic function by echocardiography; 2) peripheral vasodilator function, by measuring flow-mediated dilation (FMD) and nitrate-mediate dilation (NMD); 3) heart rate variability (HRV) on 24-h Holter electrocardiographic monitoring. RESULTS: Twenty-five patients (29.8%) had normal LV diastolic function, while 47 (55.9%) and 12 (14.3%) showed a mild and moderate/severe diastolic dysfunction, respectively. FMD in these 3 groups was 5.25 ± 2.0, 4.95 ± 1.6 and 4.43 ± 1.8% (p = 0.42), whereas NMD was 10.8 ± 2.3, 8.98 ± 3.0 and 8.82 ± 3.2%, respectively (p = 0.02). HRV variables did not differ among groups. However, the triangular index tended to be lower in patients with moderate/severe diastolic dysfunction (p = 0.09) and a significant correlation was found between the E/e' ratio and both the triangular index (r = -0.26; p = 0.022) and LF amplitude (r = -0.29; p = 0.011). CONCLUSIONS: In T2DM patients an impairment of endothelium-independent, but not endothelium-dependent, dilatation seems associated with LV diastolic dysfunction. The possible role of cardiac autonomic dysfunction in diastolic dysfunction deserves investigation in larger populations of patients.
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Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/complicações , Diástole/fisiologia , Endotélio , Ventrículos do Coração , Humanos , Função Ventricular EsquerdaRESUMO
In this work, we will investigate if red blood cell (RBC) membrane fluidity, influenced by several hyperglycemia-induced pathways, could provide a complementary index of HbA1c to monitor the development of type 2 diabetes mellitus (T2DM)-related macroangiopathic complications such as Peripheral Artery Disease (PAD). The contextual liquid crystalline (LC) domain spatial organization in the membrane was analysed to investigate the phase dynamics of the transition. Twenty-seven patients with long-duration T2DM were recruited and classified in DM, including 12 non-PAD patients, and DM + PAD, including 15 patients in any stage of PAD. Mean values of RBC generalized polarization (GP), representative of membrane fluidity, together with spatial organization of LC domains were compared between the two groups; p-values < 0.05 were considered statistically significant. Although comparable for anthropometric characteristics, duration of diabetes, and HbA1c, RBC membranes of PAD patients were found to be significantly more fluid (GP: 0.501 ± 0.026) than non-PAD patients (GP: 0.519 ± 0.007). These alterations were shown to be triggered by changes in both LC microdomain composition and distribution. We found a decrease in Feret diameter from 0.245 ± 0.281 µm in DM to 0.183 ± 0.124 µm in DM + PAD, and an increase in circularity. Altered RBC membrane fluidity is correlated to a spatial reconfiguration of LC domains, which, by possibly altering metabolic function, are associated with the development of T2DM-related macroangiopathic complications.
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Diabetes Mellitus Tipo 2 , Doença Arterial Periférica , Diabetes Mellitus Tipo 2/complicações , Eritrócitos/metabolismo , Hemoglobinas Glicadas/metabolismo , Humanos , Fluidez de Membrana , Doença Arterial Periférica/complicaçõesRESUMO
Numerous lines of research indicate that our social brain involves a network of cortical and subcortical brain regions that are responsible for sensing and controlling body movements. However, it remains unclear whether movement disorders have a systematic impact on social cognition. To address this question, we conducted a systematic review examining the influence of hyperkinetic movement disorders (including Huntington disease, Tourette syndrome, dystonia, and essential tremor) on social cognition. Following the PRISMA guidelines and registering the protocol in the PROSPERO database (CRD42022327459), we analyzed 50 published studies focusing on theory of mind (ToM), social perception, and empathy. The results from these studies provide evidence of impairments in ToM and social perception in all hyperkinetic movement disorders, particularly during the recognition of negative emotions. Additionally, individuals with Huntington's Disease and Tourette syndrome exhibit empathy disorders. These findings support the functional role of subcortical structures (such as the basal ganglia and cerebellum), which are primarily responsible for movement disorders, in deficits related to social cognition.
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Transtornos dos Movimentos , Teoria da Mente , Síndrome de Tourette , Humanos , Cognição Social , Hipercinese , Percepção Social , Cognição , EmoçõesRESUMO
Objective: Irritable bowel syndrome (IBS) is a psychosomatic gastrointestinal disorder involving the dysfunctional activation of specific brain regions crucial for interoception and disgust processing. Yet, no study has ever investigated the link between this socio-affective/visceral experience and IBS. Method: The present study investigated whether disgust sensitivity and disgust propensity, which can be socially relevant, relate with IBS symptoms in a nonclinical population.105 healthy participants were asked to complete the Disgust Propensity and Sensitivity Scale-Revised (DPSS-R), the Irritable Bowel Syndrome-Quality of Life Measure (IBS-QOL), and the Chronic Urticaria Quality of Life Measure (CU-Q2OL), as control condition. Results: Results showed higher disgust sensitivity scores in individuals with high IBS-QOL score, compared to individuals with low IBS-QOL score. The correlation analysis corroborates this result by showing a positive relationship between disgust sensitivity and respective IBS-QOL scores. Conclusions: This research provides new insights into understanding the etiopathogenesis of IBS, suggesting the relevance of a socially relevant personality trait such as disgust sensitivity as a potential trigger and / or predisposition factor for this chronic inflammatory disease.
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Myocardial bridging (MB) is the most frequent congenital coronary anomaly in which a segment of an epicardial coronary artery takes a tunneled course under a bridge of the myocardium. This segment is compressed during systole, resulting in the so-called "milking effect" at coronary angiography. As coronary blood flow occurs primarily during diastole, the clinical relevance of MB is heterogeneous, being usually considered an asymptomatic bystander. However, many studies have suggested its association with myocardial ischemia, anginal symptoms, and adverse cardiac events. The advent of contemporary non-invasive and invasive imaging modalities and the standardization of intracoronary functional assessment tools have remarkably improved our understanding of MB-related ischemia, suggesting the role of atherosclerotic lesions proximal to MB, vasomotor disorders and microvascular dysfunction as possible pathophysiological substrates. The aim of this review is to provide a contemporary overview of the pathophysiology and of the non-invasive and invasive assessment of MB, in the attempt to implement a case-by-case therapeutic approach according to the specific endotype of MB-related ischemia.
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We report the case of a 38 year-old Caucasian man enrolled in a study aimed at investigating the physical properties of red blood cells (RBCs) using advanced microscopy techniques, including Atomic Force Microscopy (AFM). At the time of his first enrolment in the study, he had normal Fasting Plasma Glucose (FPG) values, a BMI of 24.1, and no other symptoms of diabetes, including fatigue, high triglycerides, low HDL cholesterol, and altered inflammatory and corpuscular RBC indices. The subject reported no family history of diabetes, obesity, and cardiovascular diseases. Despite his apparently healthy conditions, the biomechanics of his RBCs was altered, showing increased values of stiffness and viscosity. More than 1 year after the mechanical measurements, the subject was admitted to the Operational Unit of Diabetology of the Policlinico Gemelli Hospital with high blood glucose and glycosylated hemoglobin (HbA1c) levels and diagnosed with type 1 diabetes (T1DM). Here, we show these data, and we discuss the hypothesis that RBC mechanical properties could be sensitive to changes occurring during the pre-diabetic phase of T1DM.
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Living donor kidney transplantation (LKD) has to be considered the best transplant choice for ESRD patients in terms of organ quality and survival. ABO incompatibility and positive cross-match frequently impede LKD. Recently, options based on stronger immunosuppression, apheresis techniques and Ig administration have been proposed to overcome the biological barriers. International guidelines on LKD advise paired exchange as the preferable transplant option to avoid the hazard of blood type or cross-match incompatibility. Since 1986 many paired exchange LKD programs have been started in the world including the USA, Japan, South Korea and, in Europe, the Netherlands, Switzerland, Romania, Germany and Italy. The first Italian paired exchange LKD was performed at the Pisa Transplant Center in November 2005 between three couples of spouses. One year later a National Program was established by the Italian National Transplant Center. The second experience in Italy was again in Pisa in December 2007 between two couples of spouses. International reports have shown that paired exchange LKD offers good clinical results comparable to direct LKD. In our experience paired exchange LKD is to be considered a quality choice for uremic patients, in that it allows them to obtain the benefit of an LKD that would otherwise not be practicable.
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Transplante de Rim , Doadores Vivos , Obtenção de Tecidos e Órgãos/métodos , Humanos , Itália , Obtenção de Tecidos e Órgãos/ética , Obtenção de Tecidos e Órgãos/organização & administraçãoRESUMO
Classification of the category of diabetes is extremely important for clinicians to diagnose and select the correct treatment plan. Glycosylation, oxidation and other post-translational modifications of membrane and transmembrane proteins, as well as impairment in cholesterol homeostasis, can alter lipid density, packing, and interactions of Red blood cells (RBC) plasma membranes in type 1 and type 2 diabetes, thus varying their membrane micropolarity. This can be estimated, at a submicrometric scale, by determining the membrane relative permittivity, which is the factor by which the electric field between the charges is decreased relative to vacuum. Here, we employed a membrane micropolarity sensitive probe to monitor variations in red blood cells of healthy subjects (n=16) and patients affected by type 1 (T1DM, n=10) and type 2 diabetes mellitus (T2DM, n=24) to provide a cost-effective and supplementary indicator for diabetes classification. We find a less polar membrane microenvironment in T2DM patients, and a more polar membrane microenvironment in T1DM patients compared to control healthy patients. The differences in micropolarity are statistically significant among the three groups (p<0.01). The role of serum cholesterol pool in determining these differences was investigated, and other factors potentially altering the response of the probe were considered in view of developing a clinical assay based on RBC membrane micropolarity. These preliminary data pave the way for the development of an innovative assay which could become a tool for diagnosis and progression monitoring of type 1 and type 2 diabetes.
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OBJECTIVE: Pancreas transplant alone can be effective in significantly improving the quality of life of type 1 diabetic patients, and it can also eliminate acute diabetes complications, such as hypoglycemic and/or hyperglycemic episodes. The effects of pancreas transplant alone on long-term complications of diabetes, including nephropathy, are still not settled. We evaluated whether restoration of long-lasting normoglycemia by pancreas transplant alone might have beneficial action on diabetic nephropathy. RESEARCH DESIGN AND METHODS: A total of 32 type 1 diabetic patients were evaluated before and 1 year after successful pancreas transplant alone, together with 30 matched nontransplanted type 1 diabetic subjects. Several metabolic and kidney function parameters were measured, including plasma glucose, glycohemoglobin (A1C), C-peptide, plasma lipids, blood pressure, creatinine, creatinine clearance, and urinary protein excretion. RESULTS: Pancreas transplant alone restored sustained normoglycemia, without exogenous insulin administration, and improved plasma lipid levels. Blood pressure decreased significantly. Creatinine concentrations and clearances did not differ before and after transplantation. Urinary protein excretion decreased significantly after pancreas transplant alone, with four microalbuminuric and three macroalbuminuric patients who became normoalbuminuric. None of these changes occurred in the nontransplanted group. CONCLUSIONS: Successful pancreas transplant alone, through restoration of sustained normoglycemia, improves diabetic nephropathy in type 1 diabetic patients.
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Diabetes Mellitus Tipo 1/cirurgia , Nefropatias Diabéticas/cirurgia , Transplante de Pâncreas/fisiologia , Adulto , Anticolesterolemiantes/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Glicemia/metabolismo , Peptídeo C/sangue , Colesterol/sangue , Feminino , Seguimentos , Humanos , Masculino , Proteinúria , Fatores de Tempo , Triglicerídeos/sangueRESUMO
BACKGROUND: Pancreas transplantation (PTx) with portal-enteric drainage (PED) has been associated with difficulties in respect to arterial anastomosis and graft accessibility for percutaneous biopsy. We describe a new technique that circumvents these difficulties. METHODS: Between April 2001 and April 2004, a total of 113 recipients were scheduled for PTx with PED. The superior mesenteric vein was approached from the right retroperitoneal aspect instead of from the anterior transmesenteric route. The pancreas graft was eventually placed in the right retroperitoneal space, being covered by the ascending colon and its mesentery. RESULTS: One hundred ten (97.3%) PTx were performed as planned. Systemic venous effluent was preferred in three patients because of incidental diagnosis of liver cirrhosis during surgery (n=1) and severe obesity (body mass index>35 kg/m2) (n=2). The Y iliac artery graft was kept as short as possible, and arterial anastomosis was always performed with ease. After a mean follow-up period of 21.2+/-19.9 months, the relaparotomy rate was 13.6%. No patient died after repeat surgery, and none required multiple relaparotomies. Overall, 10 grafts were lost because of acute rejection (n=3), chronic rejection (n=2), venous thrombosis (n=2), recipient death (n=2), and late (6-month) arterial thrombosis (n=1). One-year patient and graft survival were 98.1% and 90.7%, respectively. CONCLUSIONS: Our data confirm that PTx with PED is not associated with an increased risk. The technique described has distinctive technical advantages and should be included in the repertoire of PTx.
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Transplante de Pâncreas/métodos , Veia Porta , Adulto , Diabetes Mellitus Tipo 1/cirurgia , Drenagem , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Transplante de Pâncreas/mortalidade , Transplante de Pâncreas/fisiologia , Reoperação/estatística & dados numéricos , Espaço Retroperitoneal , Estudos Retrospectivos , Análise de Sobrevida , Fatores de TempoRESUMO
BACKGROUND: The effects of pancreas transplant alone (PTA) on cardiovascular risk factors (CRF) and cardiac function in type 1 diabetes mellitus (T1DM) patients are still unsettled. METHODS: We studied 13 T1DM patients who received PTA with portal drainage and 11 matched control patients. Parameters of glucose and lipid metabolism and several additional classic CRF were assessed before and up to 6 months posttransplant. Cardiac morphology and function were assessed by Doppler echocardiographic examination. RESULTS: Insulin independence was promptly achieved and then maintained after PTA. Total and low-density lipoprotein cholesterol levels were significantly lower after transplantation, whereas high-density lipoprotein cholesterol and triglyceride concentrations did not change. Both systolic and diastolic blood pressure values and fibrinogen levels improved significantly. In addition, PTA determined a significant amelioration of several morphologic and functional cardiac indices. None of the measured parameters changed in the control patients. CONCLUSIONS: PTA with portal drainage induces an early improvement of CRF and ameliorates cardiac function in patients with T1DM.
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Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 1/cirurgia , Angiopatias Diabéticas/terapia , Transplante de Pâncreas/estatística & dados numéricos , Adolescente , Adulto , Glicemia/metabolismo , Pressão Sanguínea , Colesterol/sangue , Creatinina/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Ecocardiografia , Feminino , Seguimentos , Testes de Função Cardíaca , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Triglicerídeos/sangueRESUMO
BACKGROUND: Graft shortage makes multiorgan procurement mandatory. We describe the results of a simplified method for the en bloc procurement of multiple organs, which permits isolated transplantation of all abdominal grafts, including the pancreas and the small bowel, to different recipients. METHODS: Three hundred forty-three multiorgan procurements were done with a simplified en bloc technique. RESULTS: None of the 1374 grafts that were procured sustained injuries that potentially precluded transplantation. Seventy-two grafts that were procured from 18 donors (5%) who were diagnosed with a neoplasm were discarded. Overall, 339 grafts that were procured from 325 donors were discarded because of specific contraindications, and 963 grafts (74%) were transplanted. Ninety-seven pancreata were transplanted. In 3 instances the pancreas and the small bowel were procured simultaneously and transplanted to different recipients. A total of 287 liver grafts were also transplanted at 13 different institutions. In 42 instances, the liver was not allocated to our center. Forty liver teams (95%) from 11 different institutions agreed to procure their grafts according to the simplified en bloc technique. Our team performed 18 procurements, and a surgeon from the liver transplantation team, who was assisted by one of the members of our team, performed 22 procurements. In all, 576 kidneys were transplanted, either alone or simultaneously, with other abdominal grafts at 15 different institutions. CONCLUSIONS: This procurement method has high yields, allows pancreas and small-bowel procurement, and can be learned readily.
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Abdome , Intestino Delgado/transplante , Transplante de Pâncreas , Coleta de Tecidos e Órgãos/métodos , Obtenção de Tecidos e Órgãos/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Transplante de Rim , Transplante de Fígado , Pessoa de Meia-IdadeRESUMO
The biological significance of donor-specific microchimerism (DSM) in solid organ transplantation is unresolved. It has been reported both as a favourable feature, which may facilitate induction and maintenance of tolerance, and as a sign of graft-vs-host disease. Here, we applied a quantitative real-time PCR assay (qRT-PCR) to a selected series of kidney transplant recipients to measure the level of microchimerism in relation to allograft function and survival. DSM level was assessed by scoring the HLA-DRB1 locus in 54 patients (42 males, 12 females) with more than 2 years of follow-up after transplantation; 38 patients were considered to have stable renal function (SRF) and 16 had allograft dysfunction (AD). Among patients with AD, 12 (75%) showed detectable level of microchimerism, compared to 11 (29%) SRF patients (Odds Ratio 7.36, 95% CI 1.7-35.2; p<0.01). In addition, AD patients showed a higher mean donor genome equivalents (6.5×10(-5) vs. 2.4×10(-5); p<0.001). SRF patients were re-evaluated two years later; 2 out of 27 DSM negative vs. 2 out of 11 DSM positive had lost their transplanted organ. In conclusion, qRT-PCR applied to peripheral blood shows significant association between DSM and allograft dysfunction in kidney transplant patients.
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Sobrevivência de Enxerto , Transplante de Rim , Disfunção Primária do Enxerto/sangue , Quimeras de Transplante/sangue , Feminino , Seguimentos , Humanos , Masculino , Reação em Cadeia da Polimerase em Tempo Real/métodos , Estudos Retrospectivos , Fatores de TempoRESUMO
The efficacy and safety of basiliximab, in combination with different maintenance regimens, are extensively addressed in the available literature. Basiliximab reduces the incidence of acute rejection, allows a safe reduction of steroid dosage, and is associated with economic savings, although there is substantially no proof that basiliximab prolongs either patient or graft survival. Initial basiliximab administration entails a low-risk and is associated with fewer adverse events than T cell depleting agents. However, life-threatening reactions were reported following re-exposure to basiliximab in recipients who lost graft function early after transplantation and, therefore, discontinued all immunosuppressive agents.
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Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Transplante de Rim , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/uso terapêutico , Anticorpos Monoclonais/farmacocinética , Basiliximab , Relação Dose-Resposta a Droga , Interações Medicamentosas , Farmacoeconomia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Imunossupressores/farmacocinética , Proteínas Recombinantes de Fusão/farmacocinética , Fatores de Risco , Linfócitos TRESUMO
The effects of pancreas transplantation (PTx) on diabetic retinopathy (DR) are still debated. We studied the course of DR in 48 patients (age: 40 +/- 7 years; males/females 26/22, body mass index (BMI): 23.0 +/- 2.4 kg/m2, duration of diabetes: 24 +/- 8 years) bearing a successful PTx (combined with a kidney). Follow-up ranged 6-60 months (median: 17 months). Before transplantation, according to the Eurodiab Study classification, 12 patients (25%) had nonproliferative retinopathy (NPDR; mild, moderate or severe), and 36 patients (75%) had laser-treated and/or proliferative retinopathy (LT/PDR). During the follow-up, in the NPDR group improvement/deterioration was defined as regression/progression to a lower/higher retinopathy grade; in the LT/PTD group, stabilization was defined as no new neo-vessel formation or development of new lesions requiring laser-treatment. In the NPDR group, five (41.7%) patients improved of one or more lesion grading, three (25%) patients showed no change, and four (33.3%) patients progressed of one grade. In the LT/PDR group, the post-transplant data were: stabilization in 35 (97%) patients, and worsening in one (3%) patient. The number of improved/stabilized patients was significantly higher in the transplanted than in a control group of nontransplanted type 1 diabetic patients. In conclusion, despite a relatively short follow-up period, successful PTx in our cohort of patients was associated with improvement and/or stabilization of DR in the majority of recipients.
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Retinopatia Diabética/terapia , Transplante das Ilhotas Pancreáticas , Transplante de Rim , Adulto , Glicemia/metabolismo , Estudos de Coortes , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/cirurgia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/cirurgia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We quantified the influence of delayed initiation of cyclosporine on everolimus pharmacokinetics in order to provide dosing guidance for kidney transplant patients. In a randomized multicenter study, 56 de novo kidney transplant patients received everolimus, basiliximab, corticosteroids and either immediate (n = 40) or delayed (n = 16) initiation of cyclosporine based on renal function. Everolimus and cyclosporine predose blood levels (Cmin) were obtained over the first 3 months post-transplant. Everolimus Cmin averaged 9-11 ng/mL in the immediate cyclosporine group over the first 3 months. In the delayed cyclosporine group, average everolimus Cmins were significantly lower by 2.9-fold in the absence vs. presence of cyclosporine: 2.9 +/- 2.8 vs. 8.3 +/- 3.7 ng/mL (p < 0.001). Likewise, the within-patient ratio of everolimus Cmins in the presence/absence of cyclosporine averaged 2.9 (range, 0.7-5.6). Both everolimus and cyclosporine blood concentrations need to be monitored in kidney transplant patients with delayed graft function during the period when cyclosporine is withheld and shortly after its initiation. Dosing of everolimus needs to be adjusted to take into account an average threefold increase in everolimus exposure when cyclosporine is added to the regimen.
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Ciclosporina/farmacologia , Rejeição de Enxerto/prevenção & controle , Imunossupressores/farmacologia , Imunossupressores/farmacocinética , Transplante de Rim , Rim/efeitos dos fármacos , Sirolimo/farmacocinética , Ciclosporina/sangue , Everolimo , Humanos , Sirolimo/análogos & derivados , Sirolimo/sangue , Fatores de TempoRESUMO
In this randomized controlled trial started in October 1990, 354 cadaveric kidney transplant recipients were assigned to receive either cyclosporine (CsA) monotherapy (115 patients), CsA + steroids (117 patients), or CsA + steroids + azathioprine (122 patients). The median follow-up was 85.1 mo. Thirty-one deaths occurred (infection, 12; cardiovascular disease, 11; neoplasia, 4; and others, 4), and 65 grafts were lost, mostly due to acute (15) or chronic rejection (50). The cumulative graft half-life was 18.1 yr. According to the "intention-to-treat," the 9-yr actuarial patient and graft survival were 94.0% and 73.3%, respectively, in monotherapy, 87.3% and 65.9% in dual therapy, and 87% and 72.2% in triple therapy (P = 0.647). At the last follow-up, the percentage of patients who remained with the original treatment was 51.2% in monotherapy, 81.7% in dual therapy, and 63.3% in triple therapy. At the seventh year, the mean creatinine clearances were 54.9 +/- 17.6 ml/min in monotherapy, 57.9 +/- 23.4 in dual therapy, and 60.6 +/- 20.7 in triple therapy (P = 0.375). Cataracts (P = 0.000), osteoporosis (P = 0.000), and cardiovascular complications (P = 0.000) were more frequent in dual or triple therapy than in monotherapy. Actuarial graft survival at 9 yr in patients on monotherapy who had to have steroids added was similar to that of the other two groups (62.2% versus 69.3%, P = 0.134). In conclusion, actuarial patient and graft survivals did not differ among the three schemes. The long-term renal function and survival were not affected in the patients on monotherapy who needed the addition of steroids. Monotherapy was associated with a lower incidence of extrarenal complications than the other two regimens.