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1.
Histopathology ; 75(5): 660-671, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31318463

RESUMO

AIMS: Diagnosis of primary membranous nephropathy (PMN) is mainly based on immunofluorescence/immunohistochemistry findings. However, assessment of specific features on optical microscopy can help to estimate the severity of the disease, guide treatment and predict the response. The aim of this study was to identify, classify and grade the precise histological findings in PMN to predict renal function outcome and guide treatment. METHODS AND RESULTS: Histological parameters, including focal segmental sclerosis (FSGS), tubular atrophy (TA), interstitial fibrosis (IF) and vascular hyalinosis (VH), were re-evaluated in 752 patients with PMN. Their predictive value was estimated separately, and also in a combination score (FSTIV) graded from 0 to 4. Finally, the impact of histology was assessed in the response to immunosuppressive treatment. Mean age of patients was 53.3 (15-85) years and most presented with nephrotic syndrome. FSGS was present in 32% and VH in 51% of the patients, while TA and IF were graded as stage ≥1 in 52% and 51.4%, respectively. The follow-up period was 122.3 (112-376) months. FSGS, TA and IF and VH were associated with impaired renal function at diagnosis (P = 0.02, P < 0.0001, P = 0.001 and P = 0.02, respectively) and at the end of follow-up (P = 0.004, P < 0.0001, P < 0.0001 and P = 0.04, respectively). In multiple regression and binary logistic analysis, the presence of FSGS and degree of TA were the most significant parameters predicting renal function outcome, defined either by eGFR (end), FSGS (r = 0.6, P < 0.0001) and TA (r = 0.6, P < 0.0001), or by the endpoint of >50% eGFR reduction, FSGS (P = 0.001) and TA (P = 0.02). Also, patients presented with FSGS, IF, VH and/or with FSTIV > 1 could benefit from immunosuppression, regardless of clinical presentation. CONCLUSIONS: The presence and degree of four histological indices, FSGS, VH, TA and IF, assessed separately or in combination, and FSTIV score not only predict renal function outcome after long-term follow-up, but can also help in the choice of appropriate treatment. Decisions concerning immunosuppressive treatment can be guided by pathology regardless of clinical findings.


Assuntos
Glomerulonefrite Membranosa , Nefropatias/patologia , Rim/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/terapia , Histocitoquímica , Humanos , Imunossupressores/uso terapêutico , Nefropatias/diagnóstico , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
2.
J Cell Mol Med ; 22(9): 4139-4149, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29956451

RESUMO

Chronic kidney disease, the end result of most renal and some systemic diseases, is a common condition where renal function is compromised due to fibrosis. During renal fibrosis, calreticulin, a multifunctional chaperone of the endoplasmic reticulum (ER) is up-regulated in tubular epithelial cells (TECs) both in vitro and in vivo. Proteomic analysis of cultured TECs overexpressing calreticulin led to the identification of the family of 14-3-3 proteins as key proteins overexpressed as well. Furthermore, an increased expression in the majority of 14-3-3 family members was observed in 3 different animal models of renal pathologies: the unilateral ureteric obstruction, the nephrotoxic serum administration and the ischaemia-reperfusion. In all these models, the 14-3-3σ isoform (also known as stratifin) was predominantly overexpressed. As in all these models ischaemia is a common denominator, we showed that the ischaemia-induced transcription factor HIF1α is specifically associated with the promoter region of the 14-3-3σ gene. Finally, we evaluated the expression of the family of 14-3-3 proteins and specifically 14-3-3σ in biopsies from IgA nephropathy and membranous nephropathy patients. These results propose an involvement of 14-3-3σ in renal pathology and provide evidence for the first time that hypoxia may be responsible for its altered expression.


Assuntos
Proteínas 14-3-3/genética , Biomarcadores Tumorais/genética , Exorribonucleases/genética , Glomerulonefrite por IGA/genética , Glomerulonefrite Membranosa/genética , Insuficiência Renal Crônica/genética , Traumatismo por Reperfusão/genética , Obstrução Ureteral/genética , Proteínas 14-3-3/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Calreticulina/genética , Calreticulina/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Exorribonucleases/metabolismo , Fibrose , Regulação da Expressão Gênica , Glomerulonefrite por IGA/metabolismo , Glomerulonefrite por IGA/patologia , Glomerulonefrite Membranosa/metabolismo , Glomerulonefrite Membranosa/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Isoenzimas/genética , Isoenzimas/metabolismo , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas , Proteômica/métodos , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Obstrução Ureteral/metabolismo , Obstrução Ureteral/patologia
3.
J Cell Mol Med ; 21(10): 2599-2609, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28664547

RESUMO

Renal podocytes form the main filtration barrier possessing unique phenotype maintained by proteins including podocalyxin and nephrin, which are modulated in pathological conditions. In diabetic nephropathy (DN), podocytes become structurally and functionally compromised. Nephrin, a structural backbone protein of the slit diaphragm, acts as regulator of podocyte intracellular signalling with renoprotective role. Vitamin D3 through its receptor, VDR, provides renal protection in DN but limited data exist about its effect on podocytes. In this study, we used isolated rat glomeruli to assess podocalyxin and nephrin expression after treatment with the 1,25-dihydroxyvitamin D3 analogue paricalcitol in the presence of normal and diabetic glucose levels. The role of 1,25-dihydroxyvitamin D3 (calcitriol) and its analogue, paricalcitol, on podocyte morphology and survival was also investigated in the streptozotocin (STZ)-diabetic animal model. In our ex vivo model, glomeruli exhibited high glucose-mediated down-regulation of podocalyxin, and nephrin, while paricalcitol reversed the high glucose-induced decrease of nephrin and podocalyxin expression. Paricalcitol treatment enhanced VDR expression and promoted VDR and RXR co-localization in the nucleus. Our data also indicated that hyperglycaemia impaired survival of cultured glomeruli and suggested that the implemented nephrin down-regulation was reversed by paricalcitol treatment, initiating Akt signal transduction which may be involved in glomerular survival. Our findings were further verified in vivo, as in the STZ-diabetic animal model, calcitriol and paricalcitol treatment resulted in significant amelioration of hyperglycaemia and restoration of nephrin signalling, suggesting that calcitriol and paricalcitol may provide molecular bases for protection against loss of the permselective renal barrier in DN.


Assuntos
Colecalciferol/farmacologia , Ergocalciferóis/farmacologia , Proteínas de Membrana/metabolismo , Podócitos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Conservadores da Densidade Óssea/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Glucose/farmacologia , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/metabolismo , Podócitos/metabolismo , Ratos Wistar , Sialoglicoproteínas/metabolismo , Técnicas de Cultura de Tecidos
4.
Int J Hyperthermia ; 31(8): 857-62, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26446799

RESUMO

PURPOSE: The purpose of this study is to evaluate the fluctuations of coagulation parameters during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) and confirm beyond doubt that epidural anaesthesia is safe with this type of operations. MATERIALS AND METHODS: This is a prospective clinical study of consecutive patients who had cytoreductive surgery and HIPEC. An epidural catheter was inserted into all patients. Peripheral venous blood samples in specific time points of the procedure were tested for complete blood count, prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalised ratio (INR), fibrinogen, D-dimer, and expression of the GpIIb/IIIa platelet receptor. RESULTS: A total of 51 consecutive patients were included in this study. The initial mean (SD) platelet count decreased significantly to a mean of 250.6 (105.4) 10(9)/L (p < 0.001). Fibrinogen levels decreased to 295.9 (127.4) mg/dL (p = 0.009). D-dimer levels increased to 5.3 (3.1) mg/dL (p < 0.001). APTT increased from 30.8 (5.8) s to 35.1 (4.6). The mean INR increased significantly to 1.5 (0.5) (p < 0.001). The total number of GpIIb/IIIa platelet receptors showed no significant variation throughout the measurements and was 72603.2 before HIPEC, 80772.4 during, and 77432.1 after. All the parameters examined, despite significant fluctuations remained in levels that would permit perioperative epidural analgesia. No related complications were recorded. CONCLUSION: Our results support the belief that epidural analgesia is a safe option in cytoreductive surgery and HIPEC despite certain intraoperative fluctuations in coagulation parameters. It is of major importance to regulate any abnormalities observed during surgery. There are no available data regarding the occurrence of coagulopathy in the post-operative period.


Assuntos
Analgesia Epidural , Antineoplásicos/administração & dosagem , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Neoplasias Peritoneais/terapia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Coagulação Sanguínea , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Fibrinogênio/análise , Humanos , Integrina beta3/metabolismo , Masculino , Melfalan/administração & dosagem , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Mitomicina/uso terapêutico , Neoplasias Peritoneais/sangue , Contagem de Plaquetas , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Adulto Jovem , Gencitabina
5.
Nephrol Dial Transplant ; 28(10): 2604-12, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24013682

RESUMO

BACKGROUND: For some patients with end-stage renal disease (ESRD), providing conservative care until death may be an acceptable alternative for renal replacement therapy (RRT). We aimed to estimate the occurrence of conservative care in Europe and evaluated opinions about which factors nephrologists consider important in their decision not to offer RRT. METHODS: With a web-based survey sent to nephrologists in 11 European countries, we inquired how often RRT was not started in 2009 and how specific factors would influence the nephrologists' decision to provide conservative care. We compared subgroups by nephrologist and facility characteristics using chi-square tests and Mann-Whitney U tests. RESULTS: We received 433 responses. Nephrologists decided to offer conservative care in 10% of their patients [interquartile range (IQR) 5-20%]. An additional 5% (IQR 2-10%) of the patients chose conservative care as they refused when nephrologists intended to start RRT. Patient preference (93%), severe clinical conditions (93%), vascular dementia (84%) and low physical functional status (75%) were considered extremely or quite important in the nephrologists' decision to provide conservative care. Nephrologists from countries with a low incidence of RRT, not-for-profit centres and public centres more often scored these factors as extremely or quite important than their counterparts from high-incidence countries, for-profit centres and private centres. CONCLUSIONS: Nephrologists estimated conservative care was provided to up to 15% of their patients in 2009. The presence of severe clinical conditions, vascular dementia and a low physical functional status are important factors in the decision-making not to start RRT. Patient preference was considered as a very important factor, confirming the importance of extensive patient education and shared decision-making.


Assuntos
Tomada de Decisões , Nefropatias/terapia , Nefrologia/tendências , Médicos/tendências , Padrões de Prática Médica , Diálise Renal , Terapia de Substituição Renal/tendências , Adulto , Idoso , Coleta de Dados , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
7.
Med Sci Monit ; 19: 73-80, 2013 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-23353589

RESUMO

BACKGROUND: Anesthesia and inflammatory response have been studied in major abdominal and thoracic surgical procedures, but not in major orthopaedic reconstructive procedures such as total knee arthroplasty. Most studies have compared general anesthesia with epidural anesthesia, but none has compared epidural with spinal. MATERIAL/METHODS: In a prospective randomized study, 2 groups of patients scheduled for total knee arthroplasty for osteoarthritis were evaluated regarding the inflammatory response to 2 types of regional anesthesia. In 30 patients (Group A) with spinal anesthesia followed by intravenous morphine analgesia, and in 26 patients (Group B) with epidural anesthesia followed by epidural analgesia, the inflammatory response was assessed through the calculation of leucocyte concentration (WBC), C-reactive protein (CRP), monocyte chemotactic protein 1 (MCP-1), interleukins (IL-1, IL-6, IL-10, IL-18), TNF-a, and leucocyte activation molecules CD11b and CD62l, in 3 blood samples (immediately before induction to anesthesia, immediately after closure of the operative wound, and at 24 hours post-operatively). RESULTS: The MCP-1 values showed a statistically significant increase (p<0.02) in the group of patients with spinal anesthesia. Of the leucocyte activation molecules, a high statistically significant increase was noticed in the expression of CD11b on monocytes in the sample taken 24 hours post-operatively in the patients of group A. Similarly, CD62l expression on neutrophils showed a high statistically significant reduction in the sample taken 24 hours post-operatively in the group of patients with spinal anesthesia compared to the group of patients with epidural anesthesia. CONCLUSIONS: Our results show that epidural anesthesia followed by epidural analgesia produced less inflammatory response compared with spinal anesthesia followed by intravenous morphine analgesia in patients operated on with total knee arthroplasty, and that the most sensitive markers of those investigated were the CD11b and CD62l leucocyte activation molecules.


Assuntos
Analgesia Epidural , Anestesia Epidural , Raquianestesia , Artroplastia do Joelho , Inflamação/patologia , Morfina/farmacologia , Idoso , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Citocinas/sangue , Feminino , Humanos , Injeções Intravenosas , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem
8.
Am J Kidney Dis ; 60(6): 940-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22921638

RESUMO

BACKGROUND: Little is known about the criteria nephrologists use in the decision of when to start renal replacement therapy (RRT) in early referred adult patients. We evaluated opinions of European nephrologists on the decision for when to start RRT. STUDY DESIGN: European web-based survey. PREDICTORS: Patient presentations described as uncomplicated patients, patients with unfavorable clinical and unfavorable social conditions, or patients with specific clinical, social, and logistical factors. SETTING & PARTICIPANTS: Nephrologists from 11 European countries. OUTCOMES & MEASUREMENTS: We studied opinions of European nephrologists about the influence of clinical, social, and logistical factors on decision making regarding when to start RRT, reflecting practices in place in 2009. Questions included target levels of kidney function at the start of RRT and factors accelerating or postponing RRT initiation. Using linear regression, we studied determinants of target estimated glomerular filtration rate (eGFR) at the start of RRT. RESULTS: We received 433 completed surveys. The median target eGFR selected to start RRT in uncomplicated patients was 10.0 (25th-75th percentile, 8.0-10.0) mL/min/1.73 m(2). Level of excretory kidney function was considered the most important factor in decision making regarding uncomplicated patients (selected by 54% of respondents); in patients with unfavorable clinical versus social conditions, this factor was selected by 24% versus 32%, respectively. Acute clinical factors such as life-threatening hyperkalemia refractory to medical therapy (100%) and uremic pericarditis (98%) elicited a preference for an immediate start, whereas patient preference (69%) and vascular dementia (66%) postponed the start. Higher target eGFRs were reported by respondents from high- versus low-RRT-incidence countries (10.4 [95% CI, 9.9-10.9] vs 9.1 mL/min/1.73 m(2)) and from for-profit versus not-for-profit centers (10.1 [95% CI, 9.5-10.7] vs 9.5 mL/min/1.73 m(2)). LIMITATIONS: We were unable to calculate the exact response rate and examined opinions rather than practice for 433 nephrologists. CONCLUSIONS: Only for uncomplicated patients did half the nephrologists consider excretory kidney function as the most important factor. Future studies should assess the weight of each factor affecting decision making.


Assuntos
Coleta de Dados/tendências , Tomada de Decisões , Nefropatias/terapia , Nefrologia/tendências , Médicos/tendências , Terapia de Substituição Renal/tendências , Adulto , Idoso , Coleta de Dados/métodos , Europa (Continente)/epidemiologia , Feminino , Humanos , Nefropatias/epidemiologia , Nefropatias/fisiopatologia , Testes de Função Renal/métodos , Testes de Função Renal/tendências , Masculino , Pessoa de Meia-Idade , Nefrologia/métodos , Terapia de Substituição Renal/métodos
9.
Semin Dial ; 25(3): 344-50, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22074188

RESUMO

The use of antibiotic lock solutions (ALSs) for the prevention of catheter-related blood stream infections (CRBSIs) is a promising option. The efficacy and safety of linezolid as ALS were evaluated in a randomized double-blind prospective study where 131 patients who required nontunneled catheter (NTC) for hemodialysis (HD) were randomized to receive an ALS with either (A) unfractionated heparin (2000 U/ml) alone as a catheter lock control, (B) vancomycin (5 mg/ml) + heparin (2000 U/ml), or (C) linezolid (2 mg/ml) + heparin (2000 U/ml). The primary endpoint of the study was CRBSI. A total of 152 NTCs were inserted in 131 patients. The linezolid-locked group did not present any infective episode (CRBSI rate = 0/1000 catheter days) compared with 2 episodes in the vancomycin-locked group (CRBSI rate = 1.21/1000 catheter days, p = 0.1021) and 11 episodes in the heparin-locked group (CRBSI rate = 6.7/1000 catheter days, p = 0.0001). Median number of catheter days was greater in group C (median = 38) compared with group B (median = 36, p = 0.0415) and with group A (median = 34, p = 0.0036). No side effects and no resistant organisms were recorded with the use of linezolid ALS. Linezolid appears to be a safe and effective ALS, preventing CRBSI and prolonging the survival of the catheter in HD patients.


Assuntos
Bacteriemia/prevenção & controle , Infecções Relacionadas a Cateter/prevenção & controle , Cateteres de Demora/efeitos adversos , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Vancomicina/uso terapêutico , Acetamidas , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/uso terapêutico , Bacteriemia/etiologia , Infecções Relacionadas a Cateter/etiologia , Cateteres de Demora/microbiologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Linezolida , Masculino , Pessoa de Meia-Idade , Oxazolidinonas , Estudos Prospectivos , RNA Ribossômico 23S , Diálise Renal/instrumentação , Resultado do Tratamento , Vancomicina/administração & dosagem
10.
Arch Orthop Trauma Surg ; 132(10): 1505-13, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22718076

RESUMO

INTRODUCTION: The aim of this prospective comparative study was to evaluate the serum levels of different cytokines and the frequency of adverse reactions and wound infections in patients who underwent total knee replacement (TKR) and were not transfused or received either allogeneic blood transfusion or postoperative auto-transfusion (PAT) with unwashed shed blood. MATERIALS AND METHODS: A total of 248 patients were categorized into three groups; in Group 0 (n 85) patients received no blood transfusion, in Group 1 (n 92) patients received PAT and in Group 2 (n 71) patients received allogeneic blood transfusion. Patient's demographic and clinical data including age, gender, body mass index, preoperative haemoglobin value, adverse reactions and complications were documented. The serum levels of IL-1b, IL-6, IL-8, IL-10 and TNF were measured preoperatively, and on the first, third and fifth postoperative day. A statistical analysis of the results was performed. RESULTS: A significant elevation of cytokine values were observed during the first five postoperative days in patients who received blood transfusion after TKR. Adverse reactions (chills and pyrexia) were also more common in patients who received blood transfusion, whereas superficial infections were more common in patients who received allogeneic blood transfusion. CONCLUSION: The immunological status-as expressed by the measured cytokine levels-is altered in patients receiving blood transfusion compared to patients receiving no blood transfusion during the first five postoperative days. PAT is preferable to allogeneic blood transfusion in terms of the rate of adverse reactions and superficial wound infections.


Assuntos
Artroplastia do Joelho , Transfusão de Sangue , Citocinas/sangue , Osteoartrite do Joelho/imunologia , Idoso , Artroplastia do Joelho/efeitos adversos , Citocinas/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/cirurgia , Estudos Prospectivos , Infecção da Ferida Cirúrgica/etiologia
11.
Middle East J Anaesthesiol ; 21(3): 367-73, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22428491

RESUMO

BACKGROUND: We evaluated whether the use of an intraoperative algorithm based on cerebral oximetry with near-infrared refracted spectroscopy (NIRS) monitoring, could aid in the intraoperative decision for shunt placement, in patients undergoing carotid endarterectomy (CEA). METHODS: In this prospective, randomized, controlled study were included 253 patients who underwent CEA under general anesthesia. They were randomly allocated in Group A (n=83) using NIRS monitoring and the suggested algorithm, Group B (n=84) using NIRS monitoring without the algorithm and Group C (n=86) who served as controls. Shunt placement criterion for Group A and B was 20% drop in ipsilateral regional saturation from the baseline value recorded before surgery. Primary endpoint of the study was to evaluate the use of the intraoperative algorithm based on NIRS monitoring, in the intraoperative decision for shunt placement, in patients undergoing carotid endarterectomy. Additionally, we examined whether this might affect the rate of postoperative neurologic deficits. RESULTS: When compared with Group A, Group B and Group C had 3.7 times (99% c.i. 1.5-9.5) and 70.6 times (99% c.i. 15-724.3) respectively, greater likelihood of having a shunt placed. When compared with Group B, Group C had 19.4 times (99% c.i. 4.3-191.2) greater likelihood of having a shunt placed. Regarding the rate of postoperative neurologic deficits no significant difference was found between the three groups. CONCLUSIONS: The use of a specific algorithm based on NIRS monitoring, in patients undergoing CEA, may aid in the intraoperative decision for shunt placement.


Assuntos
Algoritmos , Endarterectomia das Carótidas/métodos , Monitorização Intraoperatória/métodos , Espectroscopia de Luz Próxima ao Infravermelho , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia Geral , Gasometria , Pressão Sanguínea/fisiologia , Química Encefálica , Método Duplo-Cego , Eletrocardiografia , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/psicologia , Oxigênio/sangue , Complicações Pós-Operatórias/psicologia , Estudos Prospectivos
12.
Eur J Anaesthesiol ; 27(9): 801-6, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20679774

RESUMO

BACKGROUND AND OBJECTIVE: There is evidence from previous studies that deeper anaesthetic levels reduce postoperative pain along with analgesic requirements. The aim of this study was to confirm this observation during major urological procedures under sevoflurane anaesthesia. METHODS: Seventy ASA I or II patients undergoing radical prostatectomy or nephrectomy were randomly allocated into two groups: the L-BIS group with BIS (bispectral index scale) values kept within a range of 20-30 and the H-BIS group with values within the range of 50-60. Sevoflurane was the main anaesthetic agent used, along with inhalation of nitrous oxide and continuous remifentanil infusion. Postoperative analgesia was achieved mainly through morphine and ketamine, which was continuously infused by pump, and intravenous parecoxib. Additional analgesics (paracetamol, parecoxib and morphine) were administered in persistent (continuous, lasting longer than predicted and requiring repeated doses of analgesics) postoperative pain. The number of patients who demanded additional analgesia during the first 24 h was recorded, as well as the number of administrations performed, along with visual analogue scale (VAS) scores at 8 and 24 h. RESULTS: Sixty patients completed the study, 30 in each group. VAS scores at 8 h were significantly higher in the H-BIS group, both at rest [1 (0-4) vs. 2 (0-8), P = 0.036] and on cough [1 (0-5) vs. 2 (2-9), P = 0.021], but at 24 h were similar between the two groups. Four patients in the L-BIS group and 17 patients in the H-BIS group demanded additional analgesia (P < 0.0009), although the patients in the L-BIS group needed significantly fewer additional doses of analgesics than those in the H-BIS group [0 (0-2) vs. 1 (0-5), P < 0.0008]. CONCLUSION: The results show that intraoperative deep anaesthetic levels during major urological procedures, achieved with high sevoflurane concentrations, lead to reduced postoperative analgesic requirements.


Assuntos
Analgesia/métodos , Anestesia/métodos , Procedimentos Cirúrgicos Urológicos/métodos , Urologia/métodos , Adolescente , Adulto , Idoso , Anestesiologia/métodos , Anestésicos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Dor , Prostatectomia/métodos
13.
World J Nephrol ; 8(4): 75-82, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31523631

RESUMO

Mycophenolic acid, the active metabolite for mycophenolate mofetil and mycophenolic sodium, is a strong, noncompetitive, reversible inhibitor of inosine monophosphate dehydrogenase, the key enzyme in de novo synthesis of guanosine nucleotides leading to selective inhibition of lymphocyte proliferation. Mycophenolic acid has been evaluated as induction and remission maintenance agent in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Since the course of disease of AAV usually requires long term immunosuppression, mycophenolate has been explored as a less toxic agent compared to cyclophosphamide and azathioprine. Mycophenolate is a potent immunosuppressive agent in the therapy of AAV, non-inferior to other available drugs with comparable side effect profile. Therefore, it could be a valuable alternative in cases of toxicity with life threatening side effects or intolerance to cyclophosphamide or azathioprine, in cases with high cumulative dose of cyclophosphamide, but also in cases with insufficient response. Several studies have shown a higher relapse rate following discontinuation of mycophenolate or in mycophenolate treated subjects that raises concerns about its usefulness in the treatment of AAV. This review describes the efficacy of mycophenolate in AAV as remission induction agent, as remission maintenance agent, and as therapeutic option in relapsing AAV disease, the relapse rate following discontinuation of mycophenolate, and the adverse events related to mycophenolate treatment.

14.
PLoS One ; 14(8): e0217116, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31404062

RESUMO

INTRODUCTION: Management of the Primary Membranous Nephropathy (PMN) usually involves administration of immunosuppressives. Cyclophosphamide (Cyclo) and Calcineurin Inhibitors (CNIs) are both widely used but only limited data exist to compare their efficacy in long term follow-up. AIM: The aim of the present study was to estimate and compare long term effects of Cyclo and CNIs in patients with PMN. PATIENTS-METHODS: Clinical data, histologic findings and long term outcome were retrospectively studied. The response to treatment and rate of relapse was compared between patients treated with CNIs or Cyclo based immunosuppressive regimens. RESULTS: Twenty three centers participated in the study, with 752 PMN patients (Mean age 53.4(14-87) yrs, M/F 467/285), followed for 10.1±5.7 years. All patients were initially treated with Renin Angiotensin Aldosterone System inhibitors (RAASi) for at least 6 months. Based on their response and tolerance to initial treatment, patients were divided into 3 groups, group I with spontaneous remission, who had no further treatment, group II, continued on RAASi only, and group III on RAASi+immunosuppression. Immunosuppressive regimes were mainly based on CNIs or Cyclo. Frequent relapses and failure to treatment were more common between patients who had started on CNIs (n = 381) compared to those initially treated with Cyclo (n = 110), relapse rate: 25.2% vs. 6.4%, p<0.0001, and no response rate: 22.5% vs. 13.6%, p = 0.04, respectively. CONCLUSIONS: Long term follow up showed that administration of Cyclo in PMN is followed by better preservation of renal function, increased response rate and less frequent relapses, compared to CNIs.


Assuntos
Inibidores de Calcineurina/uso terapêutico , Ciclofosfamida/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
15.
Ren Fail ; 30(3): 261-5, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18350445

RESUMO

INTRODUCTION: Infections trigger the activation of defensive cells capable to produce and release B(2)-microglobulin (B(2)-m). Procalcitonin (PCT), secreted by a wide range of human cells, included the aforementioned defensive cells, is generally considered a sensitive and specific marker of infection. In this prospective study, we examined the possibility that infections, as detected by increased levels of PCT, increase the serum levels of B(2)-m in chronic hemodialysis (CHD) patients, possibly affecting the rate of progression of dialysis-related amyloidosis (DRA). METHODS: For a period of four months, 76 CHD patients, 45 men/31 women, mean age 63 +/- 15.7 years, with no residual renal function and in HD for 46 +/- 50 months were studied bimonthly. Blood was drawn, at baseline T(0), two months T(2), and four months T(4), for measuring hematocrit (Ht), white blood cells (WBC), erythrocyte sedimentation rate (ESR), blood urea and serum creatinine, protein (albumin, globulin), C-reactive protein (CRP), and PCT kappa alpha iota B(2)-m. Any events (especially infections) in the preceding 10-day period were recorded. RESULTS: At baseline, 100% of all B(2)-m measurements were abnormal (>2.4 mg/L), 13.4% of PCT values were increased (>1.5 ng/mL), and 49.4% of CRP values exceeded the lower limit of 5 mg/L with no statistically significant differences between the results of the three periods of the study. Statistically significant, in all periods, was the linear positive correlation of B(2)-m with PCT (T[0]: p < 0.001, T[2]: p < 0.004, T[4]: p < 0.001). Also, statistically significant (p < 0.005) was the positive correlation of B(2)-m to HD vintage. CONCLUSIONS: In this study, the strong positive correlation of B(2)-m to PCT probably signifies that the (mainly subclinical) infections increase B(2)-m production in CHD patients intensifying the problem of HD-related amyloidosis.


Assuntos
Amiloidose/microbiologia , Proteína C-Reativa/metabolismo , Calcitonina/sangue , Glicoproteínas/sangue , Falência Renal Crônica/sangue , Precursores de Proteínas/sangue , Diálise Renal/efeitos adversos , Microglobulina beta-2/sangue , Idoso , Biomarcadores/sangue , Peptídeo Relacionado com Gene de Calcitonina , Feminino , Humanos , Infecções/microbiologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
16.
Anesthesiol Res Pract ; 2018: 5135203, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30065758

RESUMO

BACKGROUND: A surgical operation in pediatric patients is a rather stressful experience for both children and their parents. The aim of this study was to assess the effect of specific demographic characteristics in parent's and children's preoperative anxiety. METHODS: The sample was composed of 128 Greek-speaking children (1-14 years of age) who had to undergo minor surgery in a University General Hospital. Before surgical operation, the Spielberger State-Trait Anxiety Inventory (STAI) questionnaire and a questionnaire for the social-demographic characteristics were completed by the parents. Children's preoperative anxiety was evaluated using the Modified Yale Preoperative Anxiety Scale (m-YPAS). RESULTS: The independent predictors of increased anxiety levels in parents are child's age (p=0.024) and gender (girls: p=0.008), living in rural areas (parents: p < 0.001; children: p=0.009), being a mother (p=0.046), high or low education level (p=0.031), a no premedicated child (p=0.007), and high baseline parental anxiety (p=0.003). Previous hospitalization (p=0.019), high situational parental anxiety (p < 0.001), no premedication (p=0.014), and being the only child in the family (p=0.045) are found to be the main determinants of preoperative anxiety control in children. CONCLUSIONS: This study identifies possible risk factors of preoperative anxiety in parents and their children, which are high parental anxiety, child's age, no premedication, being the only child in the family, living in rural areas, education level, and previous hospitalization.

17.
Clin Kidney J ; 11(1): 38-45, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29423199

RESUMO

BACKGROUND: Natural history, predisposing factors to an unfavourable outcome and the effect of various therapeutic regimens were evaluated in a cohort of 457 patients with immunoglobulin A nephropathy (IgAN) and follow-up of at least 12 months. METHODS: Patients with normal renal function and proteinuria <1 g/24 h as well as those with serum creatinine (SCr) >2.5 mg/dL and/or severe glomerulosclerosis received no treatment. Patients with normal or impaired renal function and proteinuria >1 g/24 h for >6 months received daily oral prednisolone or a 3-day course of intravenous (IV) methylprednisolone followed by oral prednisolone per os every other day or a combination of prednisolone and azathioprine. The clinical outcome was estimated using the primary endpoints of end-stage renal disease and/or doubling of baseline SCr. RESULTS: The overall 10-year renal survival was 90.8%, while end-stage renal disease and doubling of baseline SCr developed in 9.2% and 14.7% of patients, respectively. Risk factors related to the primary endpoints were elevated baseline SCr, arterial hypertension, persistent proteinuria >0.5 g/24 h and severity of tubulointerstial fibrosis. There was no difference in the clinical outcome of patients treated by the two regimens of corticosteroids; nevertheless, remission of proteinuria was more frequent in patients who received IV methylprednisolone (P = 0.000). The combination of prednisolone with azathioprine was not superior to IV methylprednisolone followed by oral prednisolone. Side effects related to immunossuppressive drugs were observed in 12.8% of patients. CONCLUSION: The clinical outcome of patients with IgAN was related to the severity of clinical and histological involvement. The addition of azathioprine to a corticosteroid-based regimen for IgAN does not improve renal outcome.

18.
Mediators Inflamm ; 2007: 27683, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17710109

RESUMO

Platelet activating factor (PAF), a potent inflammatory mediator, is implicated in several proinflammatory/inflammatory diseases such as glomerulonephritis, glomerulosclerosis, atherosclerosis, cancer, allergy, and diabetes. PAF can be produced by several renal cells under appropriate stimuli and it is thought to be implicated in renal diseases. The aim of this study is the characterization of DTT-insensitive cholinephosphotransferase (PAF-CPT) of human mesangial cell (HMC), the main regulatory enzyme of PAF de novo biosynthetic pathway. Microsomal fractions of mesangial cells were isolated and enzymatic activity and kinetic parameters were determined by TLC and in vitro biological test in rabbit washed platelets. The effect of bovine serum albumin (BSA), dithiothreitol (DTT), divalent cations (Mg2+ and Ca2+), EDTA, and various chemicals on the activity of PAF-CPT of HMC was also studied. Moreover, preliminary in vitro tests have been performed with several anti-inflammatory factors such as drugs (simvastatin, IFNa, rupatadine, tinzaparin, and salicylic acid) and bioactive compounds of Mediterranean diet (resveratrol and lipids of olive oil, olive pomace, sea bass "Dicentrarchus labrax," and gilthead sea bream "Sparus aurata"). The results indicated that the above compounds can influence PAF-CPT activity of HMC.


Assuntos
DDT/farmacologia , Diacilglicerol Colinofosfotransferase/metabolismo , Células Mesangiais/efeitos dos fármacos , Fator de Ativação de Plaquetas/metabolismo , Cálcio/farmacologia , Linhagem Celular , Ditiotreitol/farmacologia , Relação Dose-Resposta a Droga , Ácido Edético/farmacologia , Ativação Enzimática/efeitos dos fármacos , Estabilidade Enzimática/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Cinética , Células Mesangiais/citologia , Células Mesangiais/metabolismo , Soroalbumina Bovina/farmacologia , Fluoreto de Sódio/farmacologia , Sulfonas/farmacologia , Temperatura
19.
Hemodial Int ; 21(4): 498-506, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28078825

RESUMO

INTRODUCTION: Ethanol lock solution has been mainly administered in paediatric and home parenteral nutrition patients in order to prevent catheter related blood stream infections (CRBSI). Its utility in hemodialysis (HD) patients with non-tunneled-uncuffed catheter (NTC) has been poorly explored. METHODS: We conducted a prospective randomized study in chronic HD patients requiring a newly inserted NTC-while awaiting for the maturation of an already established arteriovenous fistula (AVF) or arteriovenous graft (AVG) or tunneled-cuffed catheter insertion. Patients were randomized in two groups: Group A, where the lock solution was ethanol 70% + unfractionated heparin 2000 U/mL and group B, that received only unfractionated heparin 2000 U/mL. Primary end point was CRBSIs whereas exit site infections, thrombotic and bleeding episodes were the secondary end points. FINDINGS: One hundred three HD patients were enrolled in the study (group A, n = 52; group B, n = 51). The median number of catheter days was 32 for group A (range: 23-39) and 34 (range: 27-40) for group B with no statistically significant difference between the two groups. Group A (ethanol + heparin) demonstrated 4/52 episodes (7.69%) of CRBSI whereas Group B (heparin) 11/51 episodes (21.57%) (P = 0.04). CRBSI rates per 1000 catheter days were 2.53/1000 catheter days for group A and 6.7/1000 catheter days for group B (P = 0.04). Mean cumulative infection-free catheter survival in the ethanol group did not differ significantly compared to the heparin group (log-rank test = 2.99, P = 0.08). Thrombotic episodes did not differ between the two groups. DISCUSSION: Locking of NTCs in HD patients with ethanol 70% + unfractionated heparin reduces CRBSI rates without increasing the thrombotic episodes.


Assuntos
Infecções Relacionadas a Cateter/prevenção & controle , Cateteres Venosos Centrais/efeitos adversos , Etanol/uso terapêutico , Heparina/uso terapêutico , Diálise Renal/métodos , Idoso , Infecções Relacionadas a Cateter/tratamento farmacológico , Etanol/farmacologia , Feminino , Heparina/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
20.
Int J Artif Organs ; 39(2): 87-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26953901

RESUMO

PURPOSE: More than 3 million people worldwide suffer from end-stage renal disease (ESRD). Even though regular hemodialysis is considered very costly, it is still the most commonly used method of treatment in Greece. The aim of this study is to provide a current estimate of the annual patient cost for ESRD-related regular hemodialysis, especially during a period of economic instability for Greece. METHODS: Data was collected from 113 anonymous patient files from 3 dialysis units. The cost analysis includes the following parameters: hospitalization, disposable supplies, medication, meals, contaminants, human resources and equipment depreciation/utilization. RESULTS: The cost of a regular hemodialysis session was estimated at €177.12. Human resources account for 43.53% of the hemodialysis cost, while expendable supplies and medication account for 24.79% and 21.16%, respectively. The total annual cost of ESRD per patient was calculated at €34,012.31, which breaks down into €27,630.72 (81.24%) for hemodialysis, €4,800.64 (14.11%) for hospitalization, €1,454.84 (4.28%) for laboratory tests and €126.11 (0.37%) for microsurgery. CONCLUSIONS: ESRD entails a significant economic burden for the Greek health care system. In a current context of ongoing austerity measures, which severely pressure the health care budget, further research should be performed in order to identify possible ways to reduce costs and improve management of the disease.


Assuntos
Falência Renal Crônica/terapia , Diálise Renal/economia , Efeitos Psicossociais da Doença , Custos e Análise de Custo/estatística & dados numéricos , Grécia/epidemiologia , Humanos , Falência Renal Crônica/economia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , Diálise Renal/estatística & dados numéricos , Estudos Retrospectivos
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