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1.
Contemp Clin Trials Commun ; 39: 101288, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38616815

RESUMO

Objectives: Radiation-induced dermatitis (RD) is one of the most common toxicities in radiation therapy (RT) patients. Corticosteroids, immunosuppressants, and natural products (NPs) have been used as treatment. The objective was to evaluate the efficacy of a NPs-based cream (Alantel®) to reduce the incidence of RD in women with breast cancer undergoing RT treatment. Design: We conducted a controlled, randomized, double-blind clinical trial. Setting: Radiation Oncology Unit of the Reina Sofía Hospital and 5 Primary Care centers of the Cordoba and Guadalquivir Health District (Spain). Interventions: Patients assigned to the experimental group (GTA) were treated with Alantel, while those in the control group (GTE) were treated with a moisturizer and emollient cream. Main outcome measures: The primary outcome variable was the incidence of RD. RD-free time, duration of RD, quality of life, and product safety were also assessed. Results: Seventy patients were included in the study, 35 in the GTA and 35 in the GTE. The incidence of RD was lower in the GTA (71.4%) than in the GTE (91.4%) after 4 weeks of follow-up (RR = 0.78; NNT = 5; p < 0.031). The Skindex-29 questionnaire showed differences in the statement: "My skin condition makes it hard to work or do hobbies" (17.1% in the GTE vs. 2.9% in GTA; p = 0.024). Conclusions: The higher efficacy of Alantel® compared to the control cream in reducing the incidence of RD in women with breast cancer has been demonstrated.

2.
Mol Neurobiol ; 58(9): 4639-4651, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34155583

RESUMO

The effects of the consumption of high-fat diets (HFD) have been studied to unravel the molecular pathways they are altering in order to understand the link between increased caloric intake, metabolic diseases, and the risk of cognitive dysfunction. The saturated fatty acid, palmitic acid (PA), is the main component of HFD and it has been found increased in the circulation of obese and diabetic people. In the central nervous system, PA has been associated with inflammatory responses in astrocytes, but the effects on neurons exposed to it have not been largely investigated. Given that PA affects a variety of metabolic pathways, we aimed to analyze the transcriptomic profile activated by this fatty acid to shed light on the mechanisms of neuronal dysfunction. In the current study, we profiled the transcriptome response after PA exposition at non-toxic doses in primary hippocampal neurons. Gene ontology and Reactome pathway analysis revealed a pattern of gene expression which is associated with inflammatory pathways, and importantly, with the activation of lipid metabolism that is considered not very active in neurons. Validation by quantitative RT-PCR (qRT-PCR) of Hmgcs2, Angptl4, Ugt8, and Rnf145 support the results obtained by RNAseq. Overall, these findings suggest that neurons are able to respond to saturated fatty acids changing the expression pattern of genes associated with inflammatory response and lipid utilization that may be involved in the neuronal damage associated with metabolic diseases.


Assuntos
Hipocampo/efeitos dos fármacos , Inflamação/genética , Metabolismo dos Lipídeos/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Ácido Palmítico/farmacologia , Animais , Hipocampo/metabolismo , Inflamação/metabolismo , Neurônios/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Transcriptoma
3.
Transplant Proc ; 48(9): 2880-2883, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27932097

RESUMO

BACKGROUND: Kidney transplantation is the better option for end-stage renal disease (ESRD), but for patients with human leukocyte antigen (HLA) sensitization, the wait times are significantly longer than for patients without antibodies. Many desensitization protocols have been described involving strong immunosuppression, the use of apheresis, and B-cell-modulating therapies. We have designed a desensitization protocol from day 0 for deceased donor kidney transplantation. Our aim was to present our initial experience with five kidney transplant patients. METHODS: All patients had a negative complement-dependent cytotoxicity cross-match. The desensitization protocol included five to seven doses of thymoglobulin (1.25 mg/kg) and three sessions of plasmapheresis (PP) within the first week after transplantation, with intravenous immunoglobulin (500 mg/kg) after each PP session and one dose of rituximab on day 8. The presence of donor-specific antibodies (DSA) was analyzed by use of Luminex technology; levels between 1000 and 3000 mean fluorescence intensity were considered for desensitization. RESULTS: The median age was 44 years and median renal replacement therapy time was 9 years. All recipients presented 1 to 3 DSA specificities. There were no severe side effects related to PP, infusion of intravenous immunoglobulin, or rituximab. The median follow-up period was 19.3 months. Median serum creatinine level at last follow-up was 1.7 mg/dL. A kidney biopsy was performed in all patients. Graft and patient survival was 100%. CONCLUSIONS: Until now, few data are available concerning whether HLA-incompatible kidney transplantation after desensitization would benefit patients with ERSD. The desensitization strategy using the combination of PP, low doses of intravenous immunoglobulin, and rituximab at our center resulted in a satisfactory clinical outcome.


Assuntos
Anticorpos/imunologia , Dessensibilização Imunológica/métodos , Rejeição de Enxerto/prevenção & controle , Antígenos HLA/imunologia , Transplante de Rim/métodos , Adulto , Anticorpos/análise , Soro Antilinfocitário/administração & dosagem , Esquema de Medicação , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Antígenos HLA/análise , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Imunossupressores/administração & dosagem , Rim/efeitos dos fármacos , Rim/imunologia , Rim/patologia , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Plasmaferese , Rituximab/administração & dosagem
4.
Transplant Proc ; 44(9): 2529-31, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23146444

RESUMO

BACKGROUND: The clinical significance of pretransplant donor-specific antibodies (pre-Tx DSAs) detected by single antigen bead flow cytometry (SAB-FC) remains unclear. Our aim was to investigate the impact that pre-Tx DSAs detected by SAB-FC have on the early and late clinical outcomes. PATIENTS AND METHODS: We retrospectively tested stored frozen pre-Tx sera from 222 deceased-donor kidney transplants performed between November 1997 and November 2006. All patients had a negative complement-dependent cytotoxicity (CDC) cross-match with the donor. Median follow up was 5.1 years. RESULTS: Twenty-two (10%) patients had pre-Tx HLA antibodies detected by CDC. Pre-Tx HLA antibodies were detected using SAB-FC in the sera of 46 (20.7%) patients; 36 (16.2%) of them presented pre-Tx DSAs, 18 had class I antibodies, 9 class II, and 9 patients presented both classes. Mean pre-Tx DSA class I/II was 2360/1972 (MFI) mean fluorescence index in non CDC-sensitized patients. Pre-Tx DSAs were associated with female sex, retransplants, and pretransplant transfusions. Patients with Pre-Tx DSAs more than 1000 MFI and negative CDC screening presented a higher percentage of delayed graft function (61.1% versus 38.9%), more episodes of acute vascular rejection (33.3% versus 13.7%), and chronic rejection as the cause of allograft failure (22.2% versus 9.7%) compared with non-pre-Tx DSAs patients. Five-year allograft survival was significantly worse in patients with pre-Tx DSA (68.5% versus 82%, P = .006) and in patients with pre-Tx DSA class II more than 1000 MFI (43% versus 82%, P = .009). We didn't find differences in patient survival. DISCUSSION: Pre-Tx DSAs detected by SAB-FC were more frequent in female recipients, and they were associated with acute vascular and chronic rejection and a poorer graft outcome.


Assuntos
Citometria de Fluxo , Antígenos HLA/sangue , Teste de Histocompatibilidade/métodos , Histocompatibilidade , Isoanticorpos/sangue , Transplante de Rim/imunologia , Doença Aguda , Adulto , Idoso , Biomarcadores/sangue , Doença Crônica , Testes Imunológicos de Citotoxicidade , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Espanha , Fatores de Tempo , Resultado do Tratamento
5.
Transplant Proc ; 43(6): 2154-6, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21839219

RESUMO

BACKGROUND: Anti-human leukocyte antigen antibodies (HLA Abs) have been associated with reduced kidney allograft survival. Our aim was to analyze the prevalence and impact on allograft function of donor-specific HLA antibodies (DSA) among a cohort of kidney transplant recipients. PATIENTS AND METHODS: The 321 recipients had received deceased-donor kidneys followed for a median of 70 ± 43 months. We performed a cross-sectional analysis of the presence of HLA Abs with the use of Luminex technology. RESULTS: Fifty patients (15.6%) displayed HLA Abs after transplantation including 21 (6.7%) as de novo HLA Abs. Eight patients (2.5%) developed DSA, and 42 (13%) showed no DSA. We compared 3 groups of patients: with DSA, without DSA, and without HLA sensitization. The DSA patients were younger (P = .03) with a higher percentage of men (P = .00), and having received less frequent induction treatment with basiliximab or thymoglobulin (P = .02). Patients without DSA revealed a higher percentage of pretransplantation HLA sensitization (P = .00), more pretransplantation transfusions (P = .08), and more frequent retransplantations (P = .00). The incidence of acute rejections was higher for DSA patients (P = .02) than for the other 2 groups, behaving as an independent risk factor (relative risk, 4.7; 95% confidence interval, 1.1-18.8; P = .03). Graft survival at 5 years was lower among patients with compared to those without HLA Abs (P = .00). CONCLUSIONS: HLA donor-specific sensitization, an uncommon situation in our study, was associated with younger male recipients and less induction treatment. An acute rejection episode was an independent risk factor for the development of DSA; therefore, we think that monitoring of HLA Abs should be included in evaluation of the early postransplantation period.


Assuntos
Antígenos HLA/imunologia , Histocompatibilidade , Isoanticorpos/sangue , Transplante de Rim , Adulto , Distribuição de Qui-Quadrado , Estudos Transversais , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Teste de Histocompatibilidade , Humanos , Estimativa de Kaplan-Meier , Transplante de Rim/imunologia , Transplante de Rim/mortalidade , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Espanha , Fatores de Tempo , Resultado do Tratamento
6.
Acta pediatr. esp ; 63(8): 332-335, sept. 2005. ilus
Artigo em Es | IBECS | ID: ibc-040913

RESUMO

La transmisión maternofetal es la principal causa de contagio por el virus de la inmunodeficiencia humana (VIH) en niños. La zidovudina (AZT) reduce el riesgo de transmisión vertical. La supresión de la medula ósea, incluyendo anemia y neutropenia, es el mayor efecto tóxico dosisdependiente limitante de la AZT. Excepcionalmente, se ha descrito neutropenia inducida por AZT en presencia de anticuerpos antineutrófilo en niños infectados por el VIH. En niños con infección VIH, se aprecia, con frecuencia, neutropenia como resultado de múltiples causas. La prevalencia de anticuerpos antineutrófilo es frecuente en estos pacientes, pero no parece que exista relación con la evolución a neutropenia. Hay pocos estudios sobre los efectos secundarios de la AZT en niños expuestos desde el periodo perinatal o sobre las posibles consecuencias de la exposición al VIH. Se presenta el caso de una recién nacida que recibe tratamiento para reducir la transmisión vertical por VIH y desarrolla una neutropenia en presencia de anticuerpos antineutrófilo. Esta rara complicación no ha sido descrita previamente en ningún niño expuesto de forma perinatal al VIH y tratado con zidovudina o lamivudina


Mother-to-infant transmission is the major means of infection by the human immunodeficiency virus (HIV) in children, Zidovudine (AZT) reduces the risk of vertical transmission, Bone marrow suppression, associated with disorders that include anemia and neutropenia, is the major dose-limiting toxic effect of AZT. On rare occasions, AZT-induced neutropenia in the presence of antineutrophil antibodies has been reported in HIVinfected children, Neutropenia is frequently detected in these patients and can have multiple causes. Antineutrophil antibodies are also prevalent, but their presence does not appear to correlate with the development of neutropenia. There are few studies on the secondary effects of AZT in children exposed during the perinatal period or on the possible consequences of exposure to HIV. We present the case of a newborn who, after treatment to reduce vertical HIV transmission, developed neutropenia in the presence of antineutrophil antibodies. To the best of our knowledge, this rare complication has not been reported previously in a child perinatally exposed to HIV and treated with zidovudine or lamivudine


Assuntos
Recém-Nascido , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , HIV/imunologia , Zidovudina/uso terapêutico , Neutropenia/diagnóstico , Neutropenia/terapia , Anticorpos Anticitoplasma de Neutrófilos/uso terapêutico , Estreptococos Viridans/isolamento & purificação , Citometria de Fluxo/métodos , Antibioticoprofilaxia/métodos , Teste de Coombs/métodos , Neutropenia/patologia , Neutrófilos/patologia , Neutropenia/complicações , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/tendências , Antibioticoprofilaxia
9.
Arch Otolaryngol Head Neck Surg ; 124(1): 56-9, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9440781

RESUMO

OBJECTIVE: To evaluate the use of autogenous maxillary bone for the repair of orbital floor defects secondary to blunt facial trauma. DESIGN: Retrospective case series of 41 patients with a mean follow-up of 1.7 years. SETTING: Major metropolitan teaching hospital. PATIENTS: Forty-one consecutive patients who underwent repair of orbital floor fractures with maxillary antral wall bone grafts. MAIN OUTCOME MEASURES: Presence of diplopia, orbital dystopia, implant extrusion, enophthalmos, infection, and donor site complications. RESULTS: On follow-up clinical examinations, none of the 41 patients presented with any evidence of orbital dystopia or complications relative to the implant or donor site. Two patients had persistent enophthalmos, and 4 had persistent infraorbital nerve paresthesia. Postoperative computed tomographic scans in 12 patients revealed an adequate maintenance of orbital volume without any evidence of resorption of the graft. CONCLUSION: The use of maxillary antral wall bone for the repair of orbital floor fractures is a highly reliable technique that carries minimal morbidity.


Assuntos
Fraturas Orbitárias/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Maxila , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
10.
Arch Otolaryngol Head Neck Surg ; 123(8): 823-9, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9260547

RESUMO

BACKGROUND: The desirability of restoring sensation to the upper aerodigestive tract has led to an expanded use of sensate flaps for reconstruction of mucosal defects. Sensation can be restored via preformed neural pathways through the anastomosis of recipient and donor nerves, provided that the sensate flap falls within the boundaries of the neurosome for the identified sensory nerve. OBJECTIVES: To perform detailed electrophysiologic mappings of neurosomes of potential sensate flap donor sites, to describe their variability, and to investigate the usefulness of intraoperative mapping in terms of flap design and harvesting. DESIGN: A case series of 27 patients who were undergoing free flap reconstruction of various postablative head and neck defects were examined. Two silver-silver chloride recording electrodes were placed in direct contact with the dissected sensory nerve, and the overlying skin was either mechanically or electrically stimulated. Auditory feedback, as well as visualization of the responses on an oscilloscope, determined whether the stimulated area fell within the neurosome. This technique was applied to the lateral antebrachial cutaneous nerve of the radial forearm flap (n = 15), the lateral sural cutaneous nerve of the fibula flap (n = 5), the subcostal nerve of the iliac crest flap (n = 6), and the dorsal cutaneous rami of spinal nerve T-1 or T-2 of the scapula flap (n = 1). RESULTS: The neurosome of the lateral antebrachial cutaneous nerve was relatively consistent with the variability only at the distal boundary (ie, the dorsum of the hand). The neurosome of the lateral sural cutaneous nerve was more variable, falling into 2 distinct innervation patterns: one showing innervation that was limited to the upper lateral and posterior portions of the calf and the other demonstrating significant extension into the lower half of the calf. The neurosome of the subcostal nerve showed little variability and consistently overlapped the proposed skin paddle. The neurosome of the T-1 or T-2 spinal nerve was mapped in 1 patient and is described. CONCLUSIONS: The consistency of neurosomal boundaries is dependent on the donor site. Intraoperative mapping of flap donor sites may not only assure the harvesting of a true sensate flap, but may also allow for intraoperative decision making with regard to possible modifications of flap design and harvesting techniques. Two new sensate flaps from the iliac crest and scapula are accurately described.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Neurônios/citologia , Retalhos Cirúrgicos/inervação , Adulto , Idoso , Estimulação Elétrica , Eletrofisiologia , Feminino , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Sensação , Retalhos Cirúrgicos/métodos
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