RESUMO
BACKGROUND: One daily dose of tacrolimus (QDT) improves adherence in kidney transplant (KT) recipients. A switch from twice-daily tacrolimus (BDT) to QDT showed similar efficacy and safety. METHODS: The aim of our study was to demonstrate the long-term efficacy and safety of switching from BDT to QDT in KT recipients. Preliminary results have already been published. Forty-one patients (34 men and 7 women), mean age at KT of 43.9 ± 12.7 years, underwent a 1:1 dose switch from BDT to QDT; the mean time from KT to switch was 36.6 ± 16.1 months. In our study population, 4 patients received a living donor KT and 2 received a second allograft. RESULTS: The mean follow-up was 86.8 ± 13 months from the switch and 126.2 ± 22.3 months from KT. Graft and patient survival rates were 90.2% and 95.1%, respectively. All patients maintained stable renal function during follow-up. During the first 3 months after the switch we observed a significant decrease in tacrolimus blood level (P = .0001). No significant differences were observed regarding tacrolimus dose before and after QDT introduction (P = not significant [NS]). Fourteen patients who stopped steroids under BDT treatment and 16 patients who stopped steroids after the switch are currently steroid-free. CONCLUSION: Our study showed safety and efficacy in switching from BDT to QDT. After early (<1 year) dose adjustment, tacrolimus blood levels remained stable throughout follow-up. Moreover, QDT represented a valid alternative for patients showing steroid side effects.
Assuntos
Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Transplante de Rim , Tacrolimo/administração & dosagem , Adulto , Esquema de Medicação , Feminino , Humanos , Imunossupressores/sangue , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Tacrolimo/sangueRESUMO
BACKGROUND: Mammalian target of rapamycin inhibitors (mTORi) are a promising new family of immunosuppressive drugs. No teratogenic effects have been reported to date. Their lipid and glucidic effects should not be underestimated, however, especially during pregnancy. Moreover, mTORi may affect fetal growth by mTOR placental activity. OBJECTIVE: Our purpose was to highlight mTORi placental impact and metabolic implications to detect possible maternal or fetal effects and define management guidelines in pregnant women after solid organ transplantation. METHODS: A literature search was performed for articles from the Medline and Pubmed databases with the use of the following keywords: mTOR inhibitors, pregnancy, placental transport, lipid metabolism, glucose metabolism. RESULTS: mTOR works as a positive regulator of system A, system L, and taurine placental amino acid transporter activity, which are critical for the transport of amino acids to the fetus. Exposing trophoblast cells to rapamycin reduces system L activity; therefore, treatment with rapamycin in human pregnancies could alter fetal growth with intrauterine growth restriction (IUGR). Regarding the metabolic effects mTORi increase lipolysis, impair insulin's antilipolytic effect and reduce lipid storage, which may potentially contribute to dyslipidemia. Chronic rapamycin treatment reduces adipose tissue size and ß-cell mass/function, causes hyperlipidemia, severe insulin resistance, and glucose intolerance, and promotes hepatic gluconeogenesis. CONCLUSIONS: The studies on mTORi treatment in transplanted pregnant women have not focused to date on the potential metabolic and placental effects. Selection of women at high risk for metabolic disorders could be needed and consideration of switching to another immunosuppressive drug required if diabetes and abnormal blood lipids have been diagnosed in prepregnancy counseling. It seems to be mandatory to encourage prompt reporting of any additional cases of pregnancy during mTORi exposure to provide a better understanding of the placental effects and safety profile of these immunosuppressive drugs.
Assuntos
Desenvolvimento Fetal/efeitos dos fármacos , Imunossupressores/farmacologia , Troca Materno-Fetal , Placenta/metabolismo , Transplantados , Feminino , Glucose/metabolismo , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Gravidez , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/fisiologiaRESUMO
Immunologic alterations, such as cryoglobulinemia, have been described in the acute phase of primary cytomegalovirus (CMV) infections in immunocompetent patients. There are few references about these influences of a primary CMV infection in an at-risk kidney transplant recipient (donor positive/recipient negative-D(+)/R(-)). Herein we have described the case of a 46-year-old man, who was naive for CMV and underwent renal transplantation from a CMV+ cadaveric donor, thereby at high risk for disease transmission. The immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil, and steroids. The recipient was not treated with CMV prophylaxis, but rather regularly screened for possible pre-emptive treatment. At 35 days after transplantation, he was admitted because of deep vein thrombosis (DVT) in the transplant ipsilateral lower limb accompanied by oliguria, fever, and epigastric pain accompanied by type II cryoglobulinemia and acute CMV infection. The direct antiglobulin test (DAT) for C3d was positive. The cryoglobulins displayed anti-red blood cell specificity, with maximum activity at 4°C. The DVT was successfully treated with locoregional thrombolysis in combination with anticoagulant therapy. The DAT improved with CMV treatment and increased steroid therapy. The urine output and renal function tests improved with resolution of the thrombosis, achieving complete recovery without sequelae. Our hypothesis was that CMV infection triggered cryoglobulinemia. The blood disorder caused hyperviscosity, inducing DVT. This case, of CMV infection showed associated cryoglobulinemia presenting with antierythrocyte specificity in a kidney transplant recipient.
Assuntos
Especificidade de Anticorpos , Crioglobulinemia/complicações , Infecções por Citomegalovirus/complicações , Eritrócitos/imunologia , Transplante de Rim/efeitos adversos , Trombose Venosa/complicações , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Posttraumatic stress disorder (PTSD) is characterized by the presence of anatomo-functional hippocampal alterations. To date, the ability to orient within the environment, which relies on hippocampal integrity, has never been investigated in PTSD. We hypothesized that the ability to form a cognitive map of the environment would be impaired in PTSD. Moreover, spatial memory consolidation benefits from postlearning sleep. Because PTSD individuals often complain about sleep disturbances, we hypothesized that any sleep effect on memory performance would be hampered in these subjects. Twenty-two subjects, all survivors of the L'Aquila 2009 earthquake, were divided into a PTSD and a control group, based on clinical evaluation. After an acquisition phase, they were tested twice ("test" and "retest") on a virtual navigation task. In addition, participants were administered the Digit Span and Task Switching. Subjective sleep quality and sleep disturbances were also assessed. The two testing sessions were on consecutive mornings, interspersed with a night of sleep. During the acquisition phase, the PTSD group took more than twice as long to form a cognitive map of the environment compared to the control group. However, once this phase was successfully completed, the two groups did not differ at test, but they tendentially differed at postsleep retest. Additional analyses comparing performances between groups on test-retest difference scores confirm that sleep-dependent consolidation may be differentially affected in the two groups. Our findings are strictly confined to the navigation performance, excluding a generalized cognitive deficit. PTSD also reported more subjective sleep disturbances and shorter sleep time than controls, which were correlated to worse performance at retest. The specific deficit in the formation of a cognitive map reported in PTSD may be related to hippocampal dysfunctions as well as to the sleep disturbances experienced by these patients. The possible deficiency of sleep-dependent spatial performance improvement should however be confirmed by further studies comprising a wake control group.
Assuntos
Transtornos da Memória/fisiopatologia , Memória/fisiologia , Transtornos do Sono-Vigília/fisiopatologia , Sono/fisiologia , Percepção Espacial/fisiologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adolescente , Adulto , Estudos de Casos e Controles , Terremotos , Feminino , Humanos , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/psicologia , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/psicologia , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/psicologia , Sobreviventes/psicologiaRESUMO
In order to reduce bleeding, various surgical maneuvers and devices have been used and radiofrequency (RF)-assisted liver resections have been recently advocated by many authors. We performed a right hemihepatectomy for colorectal liver metastases by using new radiofrequency generator (Surtron SB®) combined with hanging maneuver to facilitate the application of the probe and avoid injuries of the interior vena cava (IVC). Operative time was 245 minutes, intraoperative blood loss was 120 ml, transection blood loss was 70 mL. No blood units were administered at any time. After a regular postoperative (PO) course patient was discharged on 11th PO day with normal liver function tests. In conclusion combined use of a RF generator and hanging maneuver in right hemihepatectomy provide bloodless parenchymal transection. The enhanced exposure contributes to better hemostasis and permits the best allocation of the comb with protection of the IVC from injuries.
Assuntos
Ablação por Cateter/instrumentação , Ablação por Cateter/métodos , Hepatectomia , Neoplasias Hepáticas/cirurgia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Defects confined to spatial memory can severely affect a variety of daily life activities, such as remembering the location of objects or navigating the environment, until now the skills involved have been mostly assessed with regard to the visual domain using traditional pencil and paper tests. Our aim was to test the efficacy of a recently developed psychometric instrument (Walking Corsi Test: WalCT) to assess the specific contribution of spatial memory to the complex task of retrieving route knowledge. The WalCT is a 3 × 2.5-m version of the well-known Corsi Block-tapping Test (CBT), in which patients are required to memorize (and replicate) a sequence of body displacements. We assessed the ability of left and right brain-damaged patients, as well as healthy young and senior controls, to perform both the CBT and the WalCT. Results showed differences related to age in the healthy individuals and specific functional dissociations in the brain-damaged patients. The double dissociations found in this study demonstrate the importance of having a task able to detect navigational disorders, because virtual reality tasks are often much too difficult for aged brain-damaged patients to perform.
Assuntos
Lesões Encefálicas/complicações , Transtornos da Memória/etiologia , Transtornos da Percepção/etiologia , Desempenho Psicomotor/fisiologia , Comportamento Espacial/fisiologia , Percepção Visual/fisiologia , Adulto , Fatores Etários , Idoso , Mapeamento Encefálico , Feminino , Lateralidade Funcional , Humanos , Individualidade , Imageamento por Ressonância Magnética , Masculino , Rememoração Mental/fisiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estimulação Luminosa/métodos , PsicometriaRESUMO
Advagraf is a new modified-release once-daily formulation of tacrolimus. The aim of this study was to define the efficacy and safety of switching from Prograf to Advagraf immunosuppression in kidney transplant recipients. The switched dose ratio of Prograf to Advagraf was 1:1. Forty-one patients (34 men and 7 women) were switched at 36.6 ± 16.1 months after kidney transplantation. All patients maintained stable renal function and the conversion. In 16 subjects it was possible to withdraw steroid administration after obtaining adequate Advagraf blood levels, among whom 14 remained steroid free. Adverse events, including dizziness and tinnitus, were reported in 1 patient, who was reverted to Prograf. One patient who was receiving triple therapy with low tacrolimus blood levels experienced are acute rejection episode. The switch to Advagraf was safe and efficacious in kidney transplant recipients with or without steroid administration. Moreover, interruption of steroid was possible and well tolerated after achieving adequate stable blood levels with Advagraf.
Assuntos
Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Transplante de Rim , Tacrolimo/administração & dosagem , Adulto , Biomarcadores/sangue , Creatinina/sangue , Preparações de Ação Retardada , Esquema de Medicação , Monitoramento de Medicamentos , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/sangue , Itália , Transplante de Rim/imunologia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/análogos & derivados , Esteroides/administração & dosagem , Tacrolimo/efeitos adversos , Tacrolimo/sangue , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION: Breast fibroadenomas may result from exposure to cyclosporine (CsA). The aim of this prospective study was to assess the reversibility of breast fibroadenomas following conversion from CsA to tacrolimus among a small cohort of female renal transplant recipients. METHODS: Following renal transplantation, fibroadenomas either developed or progressed in eight Caucasian female patients with CsA-based immunosuppression. These patients were enrolled in a pilot study assessing whether conversion from a CsA-based to a tacrolimus-based regimen prevented progression of breast disease or reversed existing lumps. Patients underwent a baseline visit in which we assessed the clinical history, number and dimension of fibroadenomas, graft function and hormonal profile (FSH prolactin, estradiol and progesterone). Twenty-one lumps were described in six patients; in addition, two patients had "grapes of fibroadenomas," of nondefinable numbers. RESULTS: Patients underwent conversion to tacrolimus after a mean of 63.8 +/- 37.4 months after renal transplantation. Of the 21 clearly described lumps complete reversibility was observed for eight fibroadenomas. Other fibroadenomas either decreased in size or remained stable without further progression. These changes were reported within 1 year following conversion to tacrolimus. CONCLUSION: A switch from CsA to tacrolimus was effective to prevent the progression of fibroadenomas. In female renal transplant recipients with CsA-based immunosuppression suffering from breast fibroadenomas, early CsA withdrawal may avoid the need for breast surgery.
Assuntos
Neoplasias da Mama/induzido quimicamente , Ciclosporina/efeitos adversos , Fibroadenoma/induzido quimicamente , Transplante de Rim/imunologia , Tacrolimo/uso terapêutico , Adulto , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Progressão da Doença , Estradiol/sangue , Feminino , Fibroadenoma/imunologia , Fibroadenoma/patologia , Fibroadenoma/cirurgia , Hormônio Foliculoestimulante/sangue , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Transplante de Rim/patologia , Mastectomia Segmentar , Pessoa de Meia-Idade , Progesterona/sangue , Prolactina/sangue , Adulto JovemRESUMO
INTRODUCTION: Malignancies are a well-known complication of immunosuppressive therapy among renal transplant recipients, representing an important cause of long-term morbidity and mortality. Rapamycin has been shown to limit the proliferation of a number of malignant cell lines in vivo and in vitro. METHODS: Fifteen patients developed the following malignancies at a mean of 90.3 months (range = 10-252) after kidney transplantation: metastatic gastric cancer (n = 1), metastatic colon cancer (n = 1), bilateral nephrourothelioma (n = 1), skin cancer (n = 2), Kaposi's sarcoma (n = 2), posttransplant lymphoproliferative disorder (PTLD; n = 4), renal cell carcinoma T1 (n = 1), MALT lymphoma (n = 1), intramucous colon carcinoma (n = 1), liposarcoma of the spermatic cord (n = 1). After the diagnosis of malignancy, the patients were switched from calcineurin inhibitor-based immunosuppression to rapamycin (monotherapy, n = 3), or associated with steroids (n = 6) or with mycophenolate mofetil (n = 6). RESULTS: Both patients with metastatic cancer underwent chemotherapy but succumbed after 6 and 13 months. Two patients with PTLD who underwent chemotherapy died after 12 and 36 months. At a mean follow-up of 32.7 months (range = 7-56), the remaining 11 patients are cancer-free. Two patients lost their grafts after 24 and 36 months after the switch due to chronic rejection. Renal graft function remained stable in all other patients from diagnosis throughout follow-up. CONCLUSION: Our observations suggested that rapamycin-based immunosuppression offers the possibility for regression of nonmetastatic tumors. Nevertheless, it is difficult to assess whether tumor regression was due to rapamycin treatment or to the reduced immunosuppression.
Assuntos
Transplante de Rim/imunologia , Neoplasias/imunologia , Sirolimo/uso terapêutico , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Neoplasias dos Genitais Masculinos/imunologia , Neoplasias dos Genitais Masculinos/patologia , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Lipossarcoma/imunologia , Lipossarcoma/patologia , Masculino , Metástase Neoplásica , Neoplasias/epidemiologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologiaRESUMO
Herein, we report the case of a 52-year-old man with a spermatic cord liposarcoma that developed 4 years after renal transplantation. The patient was admitted with a diagnosis of inguinal hernia. During surgical exploration, a solid mass was found arising from the spermatic cord. Histologic analysis demonstrated a well-differentiated sclerosing liposarcoma.
Assuntos
Neoplasias dos Genitais Masculinos/cirurgia , Transplante de Rim/fisiologia , Lipossarcoma/cirurgia , Doenças Renais Policísticas/cirurgia , Cordão Espermático/patologia , Cordão Espermático/cirurgia , Neoplasias dos Genitais Masculinos/patologia , Hérnia Inguinal/patologia , Hérnia Inguinal/cirurgia , Humanos , Transplante de Rim/patologia , Masculino , Pessoa de Meia-Idade , Doenças Renais Policísticas/patologia , Resultado do TratamentoRESUMO
Current cognitive models suggest that the processing of dynamic facial attributes, including social signals such as gaze direction and facial expression, involves the superior temporal sulcus, whereas the processing of invariant facial structure such as the individuals' identity involves the fusiform face area. Where facial attractiveness, a social signal that may emerge from invariant facial structure, is processed within this dual-route model of face perception is uncertain. Here, we present two studies. First, we investigated the explicit judgments of facial attractiveness and attractiveness-motivated behavior in patients with acquired prosopagnosia, a deficit in familiar face recognition usually associated with damage to medial occipitotemporal cortex. We found that both abilities were impaired in these patients, with some weak residual ability for attractiveness judgments found only in those patients with unilateral right occipitotemporal or bilateral anterior temporal lesions. Importantly, deficits in attractiveness perception correlated with the severity of the face recognition deficit. Second, we performed a functional magnetic resonance imaging study in healthy subjects that included an implicit and explicit processing of facial attractiveness. We found increased neural activity when explicitly judging facial attractiveness within a number of cortical regions including the fusiform face area, but not the superior temporal sulcus, indicating a potential contribution of the fusiform face area to this judgment. Thus, converging neuropsychological and neuroimaging evidence points to a critical role of the inferior occipitotemporal cortex in the processing of facial attractiveness.
Assuntos
Discriminação Psicológica , Estética/psicologia , Face , Lobo Frontal , Prosopagnosia/fisiopatologia , Lobo Temporal , Córtex Visual , Adulto , Mapeamento Encefálico , Feminino , Lobo Frontal/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estimulação Luminosa , Prosopagnosia/psicologia , Lobo Temporal/fisiologia , Córtex Visual/fisiologia , Percepção Visual/fisiologiaRESUMO
We tested navigational abilities of brain-damaged patients suffering from representational or perceptual neglect asking them to retrieve a location according to salient spatial cues included in a rectangular empty room. Both groups of patients showed difficulties in learning the spatial definition of the target location in relation to two landmarks. However in a delayed attempt performed after several trials the group of patients with perceptual neglect proved able to easily retrieve the target location. In this condition they performed as controls showing a spared ability to navigate according to a stable representation of the room in long-term memory. In contrast the difficulty of patients with representational neglect remained unchanged across experimental conditions. At variance with clinical assessment, in which patients show asymmetrical performances in describing a well-known environment from memory, this latter result depicts a behavioural counterpart of the disorder, namely the inability to orient in a new environment according to an inner representation. Data are further discussed in order to provide a description of the cognitive mechanisms required for space representation for navigation.
Assuntos
Dano Encefálico Crônico/fisiopatologia , Sinais (Psicologia) , Orientação/fisiologia , Transtornos da Percepção/diagnóstico , Adulto , Idoso , Grupos Controle , Comportamento Exploratório/fisiologia , Feminino , Percepção de Forma/fisiologia , Lateralidade Funcional/fisiologia , Humanos , Masculino , Aprendizagem em Labirinto/fisiologia , Memória/fisiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Transtornos da Percepção/fisiopatologia , Estimulação Luminosa , Tempo de Reação/fisiologia , Percepção Espacial/fisiologiaRESUMO
Developments in functional neuroimaging in normal human subjects, such as functional magnetic resonance imaging (fMRI), have permitted the mapping of several visual areas of the human brain and have already provided provisional identification of some of the visual areas that were first described in nonhuman primates. However, the lack of a detailed description of the sulcal patterns of the human occipital lobe makes it difficult to establish clear relationships between sulcal landmarks and identified visual areas with functional neuroimaging. In the present study we used magnetic resonance images to investigate the morphological variation of the human occipital sulci in both the left and right hemispheres of 40 normal adult human brains. We identified 11 occipital sulci, the parieto-occipital fissure and the temporo-occipital incisure, and their corresponding gray matter voxels were marked in the magnetic resonance volumes which had been transformed into the Montreal Neurological Institute standard proportional stereotaxic space. Probability maps were then constructed for each occipital sulcus. These probability maps provide a quantitative measure of the variability of the occipital sulci in standard stereotaxic space and are a useful tool to identify the location of voxels of other magnetic resonance imaging images transformed in the same stereotaxic space.
Assuntos
Mapeamento Encefálico/métodos , Lobo Occipital/anatomia & histologia , Lobo Occipital/fisiologia , Técnicas Estereotáxicas , Adulto , Feminino , Lateralidade Funcional/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Modelos Anatômicos , Modelos Estatísticos , Caracteres Sexuais , Córtex Visual/anatomia & histologia , Córtex Visual/fisiologiaRESUMO
This study investigated the impact of specific cytokine genotypes on the incidence of acute rejection episodes (ARE), chronic graft dysfunction (CGD), and anti-HLA donor-specific antibody (DS-Ab) production in 86 renal transplant recipients and 70 cadaveric donors. A PCR-SSP method was performed for the analysis of polymorphisms in TNF-alpha, IL-6, TGF-beta, IL-10, and IFN-gamma cytokines. DS-Ab monitoring of sera was performed using a FCXM analysis. Observed cytokine frequencies for patients and donors were not significantly different from the expected frequencies under Hardy-Weinberg equilibrium conditions. The evaluation in recipients revealed a higher frequency of DS-Ab-positive patients among the TNF-alpha high (50.0% vs 25.7%), and for the IL-10 cytokine a greater incidence of ARE-positive patients (35.8% vs 18.2%) with the high + intermediate, compared with the low genotype. The combined effect of these 2 genotypes predisposed to DS-Abs (71.4% vs 25.3%; P = 0.02; odds ratio [OR] = 7.37). As for the TGF-beta1 cytokine, we observed a higher number of CGD-positive patients among high compared with intermediate producers (14.3% vs 0%; P = .050). The analysis of donors revealed a significantly lower incidence of ARE-positive patients among recipients whose donors were carriers of the high IL-6 G/G-genotype compared with the G/C+C/C-genotypes (16.7% vs 41.2%; P = .03), suggesting a protective effect of the G/G genotype on ARE and a predisposing role of donor (-174)allele C. In addition, we noted an association between the IFN-gamma low A/A-genotype and a higher incidence of ARE (42.1% vs 0%; P = .002) and DS-Ab production (47.4% vs 12.5%; P = .02) compared with high producers.
Assuntos
Citocinas/genética , Transplante de Rim/imunologia , Doadores de Tecidos , Autoanticorpos/sangue , Cadáver , Genótipo , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/genética , Antígenos HLA/sangue , Humanos , Interferon gama/genética , Doadores Vivos , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Transplante Homólogo/imunologiaRESUMO
INTRODUCTION: Malignancies are a well-known complication of immunosuppressive therapy among renal transplant recipients, representing an important cause of long-term morbidity and mortality. Rapamycin has been shown to limit the proliferation of a number of malignant cell lines in vivo and in vitro. METHODS: Eight patients developed the following malignancies after kidney transplantation (mean 102.6 months; range 12 to 252): metastatic gastric cancer (n = 1), metastatic colon cancer (n = 1), bilateral nephrourothelioma (n = 1), skin cancer (n = 1), Kaposi's sarcoma (n = 2), posttransplant lymphoproliferative disorder (PTLD) (n = 2). After the diagnosis of malignancy, the patients were switched from calcineurin inhibitor-based immunosuppression to rapamycin (monotherapy, n = 2), associated with steroids (n = 4) or mycophenolate mofetil (n = 2). RESULTS: Both patients with metastatic cancer underwent chemotherapy and then succummbed after 6 and 13 months. After a mean follow-up of 20.3 months (range 2 to 47), the remaining six patients are free from cancer disease. Renal graft function was unchanged from diagnosis throughout the follow-up. CONCLUSION: Our observations suggested that rapamycin-based immunosuppression offered the possibility of regression of nonmetastatic tumors. Nevertheless, it is difficult to assess whether tumor regression was attributed to Rapamycin treatment or to the reduced immunosuppression.
Assuntos
Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Neoplasias/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Sirolimo/uso terapêutico , Humanos , Neoplasias/imunologia , Neoplasias/prevenção & controleRESUMO
The aim of the study was to evaluate safety and efficacy of everolimus with cyclosporine (CsA) in de novo renal transplant recipients. The immunosuppressive regimen, including basiliximab, everolimus (3 mg), and low-dose CsA, was administered to 17 patients, of whom 15 were part of a multicenter randomized study that stipulated cessation of steroids at 7 days posttransplantation in 5 recipients. Five patients underwent dialysis after transplantation for delayed graft function (DGF; 29%), all of whom showed a good recovery within 3 weeks. The mean follow-up was 45.7 months (SD +/- 13). The 1-year graft survival was 100%. We observed one acute rejection episode. No patient experienced a cytomegalovirus infection. Increased cholesterol and triglyceride levels were reported in almost all patients. Severe arthralgia (n = 3) was treated by everolimus dose reduction to maintain trough levels at 3 ng/mL. We noted a high rate of switch to mycophenolate mofetil (MMF) throughout follow-up (n = 7), due to everolimus-induced side effects. However, we did not observe normalization of lipids after the switch: patients always required stain treatment, resulting in slightly lower serum cholesterol and triglycerides. Everolimus plus CsA was effective to prevent acute rejection after kidney transplantation. To manage the induced side effects of the drugs C(2) monitoring is mandatory, targeting 350 ng/mL during 1 year and 200 to 250 ng/mL thereafter. Careful reduction of everolimus trough levels to 3 ng/mL is recommended for patients with arthralgia.
Assuntos
Ciclosporina/uso terapêutico , Sobrevivência de Enxerto/imunologia , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Sirolimo/análogos & derivados , Adulto , Idoso , Quimioterapia Combinada , Everolimo , Feminino , Seguimentos , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Nefropatias/classificação , Nefropatias/cirurgia , Masculino , Pessoa de Meia-Idade , Sirolimo/uso terapêutico , Fatores de TempoRESUMO
The hemolytic uremic syndrome (HUS) is a severe disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. We herein report our experience with a 43-year-old female patient who underwent a second cadaveric kidney transplantation in February 2005, for adult-onset HUS. The first renal transplantation, which was performed in 1996, required removal after 3 weeks for probable recurrence of HUS. The immunosuppressive regimen for the second transplant included basiliximab, tacrolimus, mycophenolate mofetil, and steroids. On postoperative day (POD) 7, she received steroid treatment for an acute rejection episode with improved renal function. On POD 19 due to worsening renal function, a graft biopsy showed HUS recurrence, thus we instituted hemodialysis and then plasmapheresis treatments. At two months after transplantation, the patient continued under plasmapheresis treatment due to clinical evidence of HUS. On POD 80, cytomegalovirus infection was diagnosed and intravenous gancyclovir treatment started for 3 weeks. After 110 days from transplant, a deterioration in renal function was evident: the graft was swollen and painful with Doppler ultrasound showing patency of both the renal artery and vein but, low blood flow. After 2 weeks of hemodialysis, the patient underwent transplantectomy. In adult-onset HUS the recurrence rate reduces graft survival, particularly among patients undergoing second transplantation.
Assuntos
Síndrome Hemolítico-Urêmica/diagnóstico , Síndrome Hemolítico-Urêmica/cirurgia , Transplante de Rim/efeitos adversos , Adulto , Feminino , Humanos , Plasmaferese , Recidiva , Diálise Renal , Reoperação , Falha de Tratamento , Resultado do TratamentoRESUMO
The training of the transplant surgeon is one of the most difficult paths in medicine. The transplant surgeon must be trained as a general and a vascular surgeon; he has to be skilled and upgraded in transplant surgical technique; he has to decide the suitability of the donor and of the organs as well as the immunosuppressive therapy for each recipient; he must know the intensive care unit, hepatology, and nephrology. The transplant surgeon has to deal with surgical, infectious, and metabolic complications after organ transplantation. Thus, clinical formation of the transplant surgeon is multifactorial and always upgraded. However, transplants never happen in the morning; retrivals are more likely to be in the night (especially the holidays ones). "Weekend" is a word not frequently used by transplant surgeons. Moreover, when the transplant procedure happens, the normal activity of the ward and of the outpatient clinic were have to be done. The transplant surgeon must have a sort of "vocation" for such a job. Organ harvesting setting is a good proof of adaptability, always during nighttime, often in small hospitals with operating room nurses unfamiliar with the procedure, sometimes waiting for some colleagues or delaying the surgery. This vocation is enhanced by enthusiasm, but incentives are necessary to feed this love. Incentives should be professional and economic; transplant surgeons should be allowed to make clinical decisions, to choose the surgical technique of transplantation, to control the decision process. Lastly, due to the "total on call," the surgeon should profit from a right salary avoiding extramural activities.
Assuntos
Motivação , Ocupações , Especialidades Cirúrgicas/tendências , Transplante/tendências , Adulto , Humanos , Masculino , Especialidades Cirúrgicas/economiaRESUMO
The aim of this study was to estimate the incidence of infectious diseases in a group of patients who underwent kidney transplantation from January 1, 2004 to September 30, 2004, including 121 operations, with 119 from cadaveric and 2 from living donors. The protocol sought herpes viruses (CMV, VZV, and EBV), hepatitis viruses, human immunodeficiency virus, T. gondii, M. tubercolosis, and T. pallidum. Therapy for CMV was used both as prophylaxis in immunoglobulin (Ig)G-negative recipients from IgG-positive donors and preemptive therapy, that is, before the appearance of clinical symptoms, but after viremia reached borderline levels. For VZV infections, the treatment started after the appearance of papulo-vesicular cutaneous eruptions and antibody positivity. The treatment for pneumonia consisted of empirical therapy after radiography; for pyelonephritis, antibiotic therapy was based on the results of kidney echography, blood culture, and urine culture. Infectious complications appeared in 25 patients (20.7%), 3 of the which were polymicrobic: 12 CMV infections, 9 VZV infections, 3 pneumoniae, 4 pyelonephritis, and 1 salmonellosis. The most frequent infection was CMV, which occurred in the first 3 months after transplantation in 9 of 12 cases. This study showed that a knowledge of infection prevalence can help the physician to establish a more specific, efficacious antimicrobial therapy, despite the laboratory response not being available in a short time.
Assuntos
Infecções/epidemiologia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Infecções Bacterianas/epidemiologia , Controle de Doenças Transmissíveis/métodos , Infecções por Citomegalovirus/epidemiologia , Humanos , Prevalência , Viroses/epidemiologiaRESUMO
Urologic complications in kidney transplantation have an incidence ranging from 3% to 20%, representing an important cause of organ loss. From January 2001 to September 2004, 123 renal transplantations were performed using an immunosuppressive protocol including basiliximab, mycophenolate mofetil, calcineurin inhibitors, and steroids. The surgical technique was vascular anastomoses to external iliac vessels, and ureteral anastomosis according to Lich Gregoire technique using a JJ ureteral stent. We report 5 renal complications (4.2%) and 4 extrarenal complications (3.5%), the majority of which required corrective surgery. The surgical strategy uses the clinical condition of the donor and the recipient; the anatomic anomalies of the graft, and a reduced cold ischemia time. Moreover, a reduction in acute rejection episodes and immediate renal function has been fundamental to reduce urologic complications. In fact, the main cause of urologic complications is ureteral ischemia, linked both to backtable surgery and to rejection episodes. Another important factor in the reduction of early urologic complications has been the routine use of a JJ stent, which allowed us a conservative approach in this setting.