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1.
Burns ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39127577

RESUMO

AIM: This study aims to develop an experimental treatment model effective against oxidative stress in the acute period of severe burns and to analyze the mechanisms of healing large wound defects. METHODS: Five rats, including 2 females and 3 males, were used as donors to obtain adipose-derived stem cells (ADSC) from the inguinal fat pad. The stem cells were labeled with green fluorescent protein. The study included four groups of 17 rats, each with grade 3 scalding burns on 30 % of their body surface, and a control group of 10 rats with an equal number of males and females. After early excision, 106 ADSC-derived stem cells were administered subdermally to the burned wound and autografted to the stem cell group (n = 17). The early excision group (n = 17) received early excision and autograft, with 2 ml of normal saline injected subdermally into the burn wound edge. The PLM group (n = 17) was treated with a polylactic membrane (PLM) dressing after the burn. No treatment was given to the burn group (n = 17). Ten rats from all groups were sacrificed on the 4th day post-burn for oxidative stress evaluation. The control group (n = 10) was sacrificed on day 4. Blood and tissue samples were collected post-sacrifice. Oxidative stress and inflammation in the blood, as well as cell damage in the skin, liver, kidneys, and lungs, were investigated histopathologically and biochemically on the 4th day post-burn. On the 70th day after burn, wound healing was examined macroscopically and histopathologically. RESULTS: On the 4th day, oxidative stress results showed that the levels of Total Oxidative Capacity (TOC) in the blood were lowest in the stem cell (7.4 [6-8.8]), control (6.7 [5.9-7.6]), and early excision (7.5 [6.6-8.5]) groups, with no significant difference between them. The burn group (14.7 [12.5-16.9]) had the highest TOC levels. The PLM group (9.7 [8.6-10.7]) had lower TOC levels than the burn group but higher levels than the other groups. Histopathological examination on the 4th day revealed low liver caspase-3 immunoreactivity in the stem cell and early excision groups among the burn groups. Caspase-3 immunoreactivity levels were as follows: stem cell group (20 [10-30]), early excision group (25 [15-50]), PLM group (70 [50-100]), control group (0), and burn group (80 [60-120]). Other oxidative stress and end-organ damage outcomes were consistent with these results. All rats in the stem cell group had burn wounds that healed completely by the 70th day. Examination of the skin and its appendages from the stem cell group with an immunofluorescence microscope demonstrated green coloration, indicating incorporation of stem cells. CONCLUSION: Stem cells may have the potential to form new skin and its appendages, providing better healing for large skin defects. Early excision treatment, by removing local necrotic tissues after extensive and deep burns, can prevent end-organ damage due to systemic oxidative stress and inflammation. We also believe that when these two treatments are used together, they can achieve the best results.

2.
Turk Kardiyol Dern Ars ; 52(5): 352-356, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38982817

RESUMO

Dual antiplatelet therapy (DAPT) is a vital part of the pharmacological management in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). While early discontinuation of DAPT increases ischemic risk, some patients on DAPT may require urgent surgery, necessitating its interruption. Cangrelor, an intravenous P2Y12 antagonist, provides strong platelet inhibition within minutes and platelet activity normalizes within one hour after the cessation of the drug. Bridging antiplatelet therapy with cangrelor has been increasingly studied as an alternative option to ensure the continuation of platelet inhibition in CAD patients who require discontinuation of DAPT. The present patient, with a recent history of PCI for acute coronary syndrome, experienced a significant esophageal perforation following transesophageal echocardiography (TEE). This severe complication was effectively managed endoscopically, and as part of the recent PCI treatment, prolonged cangrelor infusion was successfully utilized with no thrombotic or bleeding events throughout the management of the complication.


Assuntos
Síndrome Coronariana Aguda , Monofosfato de Adenosina , Ecocardiografia Transesofagiana , Perfuração Esofágica , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Humanos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/administração & dosagem , Síndrome Coronariana Aguda/terapia , Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/administração & dosagem , Masculino , Idoso , Pessoa de Meia-Idade
3.
Drug Chem Toxicol ; 47(5): 516-526, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38726977

RESUMO

Tenofovir alafenamide (TAF) is a new drug from the nucleotide reverse transcriptase inhibitor group approved for the treatment of chronic Hepatitis B in 2016. With this study, we aimed to test whether possible cellular toxicity can be reduced by controlled drug release as a result of loading with chitosan nanoparticles (CHS). We investigated the genotoxic and mitotoxic effects of 45 µM TAF-loaded CHS and TAF-only on HepG2 cells by micronucleus (MN), comet assay, determination of mtDNA quantification, mitochondrial membrane potential (ΔΨm), and ROS levels. Additionally, we compared the samples by RNAseq analyses to reveal the transcriptional responses to each regimen. In terms of genotoxic tests, although MN and comet were found higher in all experimental treatment conditions, the encapsulation of CHS reduced the genotoxicity of TAF. MtDNA level was found to be lower in the TAF treatment, whereas it was higher in CHS and CHS-TAF treatments. The TAF-loaded CHS and TAF treatments had an impaired ΔΨm value. Cellular ROS levels were higher in all treatment conditions. According to the analyses of gene expression patterns; CHS-only changed the expression of relatively few genes (187 genes), while TAF changed the expression of the 1974 genes and TAF-loaded CHS changed the expression of 734 genes. Considering the gene expression numbers, CHS encapsulation of TAF significantly reduced the number of genes that were differentially expressed by TAF-only. Overall, we observed that TAF has genotoxic and mitotoxic effects on HepG2 cells, and upon encapsulation with CHS, its genotoxic and mitotoxic effects were decreased.


Assuntos
Quitosana , Dano ao DNA , Potencial da Membrana Mitocondrial , Testes para Micronúcleos , Nanopartículas , Espécies Reativas de Oxigênio , Tenofovir , Humanos , Quitosana/química , Células Hep G2 , Nanopartículas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Tenofovir/toxicidade , Tenofovir/administração & dosagem , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Ensaio Cometa , DNA Mitocondrial/efeitos dos fármacos , Portadores de Fármacos/química , Preparações de Ação Retardada , Inibidores da Transcriptase Reversa/toxicidade
4.
Turk Arch Pediatr ; 58(5): 531-538, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37670552

RESUMO

OBJECTIVE: Despite marked improvements in the accessibility of childhood vaccines, knowledge gaps remain about the vaccination of children in special risk groups (SRG). This study aimed to analyze the clinical data of children vaccinated in SRG in a single-center unit to contribute to the clinical evidence for the specific planning of immunization of children in SRG. The second- ary aim is to present institutional consensus on the vaccination of children in SRG. MATERIALS AND METHODS: This retrospective study was conducted at a single-center pediatric vaccination clinic. Patient charts between 2018 and 2021 were retrospectively reviewed, and clinical and laboratory data were extracted. Serial joint meetings with multiple healthcare pro- fessionals were performed to develop an institutional protocol for vaccination. RESULTS: There were 479 children vaccinated between 2018 and 2021 for reasons such as post- chemotherapy, after hematopoietic stem cell transplantation, before/after solid organ trans- plantation, allergies, and chronic diseases. Of these, 298 (62.2%) children vaccinated in the unit due to a history of food or vaccine allergies were excluded. One hundred eighty-one children were vaccinated at a median age of 11 [7-15] years. Most children were vaccinated after treat- ment for malignancies. Solid tumors were the most frequent malignancy (67%), followed by acute lymphoblastic leukemia (29.0%) and acute myeloid leukemia (4.0%). Institutional vacci- nation protocols for cancer survivors, hematopoietic stem cells, and solid organ recipient chil- dren were developed and presented. CONCLUSION: There is a need to prepare national guidelines for vaccinating children with altered immunocompetence. Sharing vaccination practices by multidisciplinary vaccination units might increase and provide knowledge to develop national policies.

5.
Mol Biol Rep ; 50(10): 8551-8563, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37644370

RESUMO

BACKGROUND: Liver cancer is the third leading cause of cancer-related deaths worldwide, and hepatocellular carcinoma (HCC) is the most common type of liver cancer. Transarterial interventions are among the chemotherapeutic approaches used in hardly operable regions prior to transplantation, and in electrochemotherapy, where doxorubicin is used. However, the efficacy of treatment is affected by resistance mechanisms. Previously, we showed that overexpression of the CUE5 gene results in doxorubicin resistance in Saccharomyces cerevisiae (S. cerevisiae). In this study, the effect of Toll-interacting protein (TOLLIP), the human ortholog of CUE5, on doxorubicin resistance was evaluated in HCC cells to identify its possible role in increasing the efficacy of transarterial interventions. METHODS AND RESULTS: The NIH Gene Expression Omnibus (GEO) and Oncomine datasets were analyzed for HCC cell lines with relatively low and high TOLLIP expression, and SNU449 and Hep3B cell lines were chosen, respectively. TOLLIP expression was increased by plasmid transfection and decreased by TOLLIP-siRNA in both cell lines and evaluated by RT-PCR and ELISA. Cell proliferation and viability were examined using xCELLigence and MTT assays after doxorubicin treatment, and growth inhibitory 50 (GI 50) concentrations were evaluated. Doxorubicin GI 50 concentrations decreased approximately 2-folds in both cell lines upon silencing TOLLIP after 48 h of drug treatment. CONCLUSIONS: Our results showed for the first time that silencing TOLLIP in hepatocellular carcinoma cells may help sensitize these cells to doxorubicin and increase the efficacy of chemotherapeutic regimens where doxorubicin is used.


Assuntos
Carcinoma Hepatocelular , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias Hepáticas , Humanos , Apoptose , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Saccharomyces cerevisiae , Peptídeos e Proteínas de Sinalização Intracelular/genética
6.
Leuk Lymphoma ; 64(7): 1304-1314, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37165575

RESUMO

The St Jude Total Therapy Study XV was the first clinical trial to prospectively use minimal residual disease levels during and after remission induction therapy to guide risk-directed treatment. We used the Total Therapy XV protocol with minimal modification in treating 115 newly diagnosed pediatric acute lymphoblastic leukemia patients from low- and middle-income groups from January 2011 to December 2017. The mean age at diagnosis was 5.97 ± 3.96 years. The median follow-up period was 88 months. Three (2.6%) patients had bone marrow relapse, and one (0.87%) had an isolated central nervous system relapse. Nineteen of the patients (16.52%) died due to infection-related complications, three (2.61%) died due to progressive disease, and one (0.87%) died due to hematopoietic stem cell transplant complications. Five-year overall survival was 80%, and event-free survival was 78.3%. Our results showed that the Total XV treatment protocol could be used successfully in patients with ALL from low- and middle-income populations. However, infection-related deaths remain a significant problem.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Lactente , Pré-Escolar , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Terapia Combinada , Recidiva , Indução de Remissão , Resultado do Tratamento
7.
Braz. j. otorhinolaryngol. (Impr.) ; 88(supl.3): 25-33, Nov.-Dec. 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1420836

RESUMO

Abstract Objective: Vestibular Migraine (VM) is the second most common cause in patients with vertigo. Patients with VM complain about vestibular symptoms during a headache attack or during the period between attacks. Vestibular Rehabilitation (VR), an exercised based therapy to treat dizziness and balance dysfunction has been shown to be effective in vestibular diseases. In this study, we aimed to assess the effect of VR for vestibular symptoms and quality of life in VM patients, and to compare the results with patients with vestibular disorders without migraine. Methods: Sixty (60) patients who received VR treatment were divided into two groups: vestibular migraine group (30 patients) and non-migraine vestibular dysfunction group (30 patients). All patients received VR for 18 sessions and the program was completed in 1.5 months. Preand post-treatment Dizziness Handicap Inventory (DHI) scores, Vestibular Disorders Activities of Daily Living Scale (VADL) scores, the frequency of dizziness and headache, and Computerized Dynamic Posturography (CDP) scores were assessed and compared retrospectively. Results: With VR in both the vestibular migraine group and vestibular dysfunction group, DHI score, VADL score, the frequency of dizziness and headache scores significantly impaired. Post-treatment CDP results were higher than pre- treatment results for both patient groups. Conclusion: With VR, a significant improvement was observed in subjective and objective balance assessment measurement. Vestibular Rehabilitation must be considered in patients who do not benefit from medical therapy or have limited benefit. Level of evidence: Level III (evidence obtained from well-designed controlled trials without randomization).

8.
Microbiologyopen ; 11(3): e1284, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35765185

RESUMO

Arsenic is a toxic metalloid that affects human health by causing numerous diseases and by being used in the treatment of acute promyelocytic leukemia. Saccharomyces cerevisiae (budding yeast) has been extensively utilized to elucidate the molecular mechanisms underlying arsenic toxicity and resistance in eukaryotes. In this study, we applied a genomic DNA overexpression strategy to identify yeast genes that provide arsenic resistance in wild-type and arsenic-sensitive S. cerevisiae cells. In addition to known arsenic-related genes, our genetic screen revealed novel genes, including PHO86, VBA3, UGP1, and TUL1, whose overexpression conferred resistance. To gain insights into possible resistance mechanisms, we addressed the contribution of these genes to cell growth, intracellular arsenic, and protein aggregation during arsenate exposure. Overexpression of PHO86 resulted in higher cellular arsenic levels but no additional effect on protein aggregation, indicating that these cells efficiently protect their intracellular environment. VBA3 overexpression caused resistance despite higher intracellular arsenic and protein aggregation levels. Overexpression of UGP1 led to lower intracellular arsenic and protein aggregation levels while TUL1 overexpression had no impact on intracellular arsenic or protein aggregation levels. Thus, the identified genes appear to confer arsenic resistance through distinct mechanisms but the molecular details remain to be elucidated.


Assuntos
Arsênio , Proteínas de Saccharomyces cerevisiae , Arsênio/metabolismo , Arsênio/toxicidade , Humanos , Agregados Proteicos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
10.
Beyoglu Eye J ; 6(3): 223-228, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35005520

RESUMO

OBJECTIVES: The goal of this study was to evaluate surgical techniques and outcomes in patients with Brown's syndrome. METHODS: A retrospective review was conducted of patients who underwent surgery of the superior oblique (SO) muscle between 2003 and 2011 at a referral center. RESULTS: In all, 190 patients (111 female and 79 male) with an age range of 4-50 years were included in the study. The right eye was affected in 98 patients, and the left eye in 92 patients. Abnormal head posture (AHP), ocular movement (OM), and hypotropia were assessed. The greatest improvement of AHP was seen following an SO temporal tenotomy (91%). Patients with a -4 limitation achieved full OM after a SO temporal tenotomy. CONCLUSION: Temporal tenotomy provided the best improvement in limitation of elevation in adduction.

11.
Pediatr Blood Cancer ; 67(2): e28091, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31736244

RESUMO

BACKGROUND: Regarding the difficulties in recognition and management of the malignancies in primary immune deficiencies (PIDs), we aimed to present the types, risk factors, treatment options, and prognosis of the cancers in this specific group. METHODS: Seventeen patients with PID who developed malignancies or malignant-like diseases were evaluated for demographics, clinical features, treatment, toxicity, and prognosis. RESULTS: The median age of malignancy was 12.2 years (range, 2.2-26). Lymphoma was the most frequent malignancy (n = 7), followed by adenocarcinoma (n = 3), squamous cell carcinoma (n = 2), cholangiocarcinoma (n = 1), Wilms tumor (n = 1), and acute myeloid leukemia (n = 1). Nonneoplastic lymphoproliferation mimicking lymphoma was observed in five patients. The total overall survival (OS) was 62.5% ± 12.1%. The OS for lymphoma was 62.2% ± 17.1% and found to be inferior to non-PID patients with lymphoma (P = 0.001). CONCLUSION: In patients with PIDs, malignancy may occur and negatively affect the OS. The diagnosis can be challenging in the presence of nonneoplastic lymphoproliferative disease or bone marrow abnormalities. Awareness of susceptibility to malignant transformation and early diagnosis with multidisciplinary approach can save the patients' lives.


Assuntos
Tecido Linfoide/patologia , Linfoma/classificação , Linfoma/diagnóstico , Doenças da Imunodeficiência Primária/complicações , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Linfoma/etiologia , Linfoma/terapia , Masculino , Doenças da Imunodeficiência Primária/patologia , Prognóstico , Taxa de Sobrevida , Adulto Jovem
12.
J Pediatr Surg ; 55(3): 465-474, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31109733

RESUMO

INTRODUCTION: Parenteral nutrition (PN) is used for the intravenous delivery of nutrients to patients who cannot take food orally. However, it is not clear whether PN also negatively impacts cardiac tissue. The present empirical study investigated the cardiac effects of PN in rabbits. METHODS: The effects of PN were examined in three groups of rabbits: animals in the PN + fasting group (n = 14) had been fully fasted before receiving a full PN dose via an intravenous central catheter; the PN + oral feeding group (n = 14) received half of the daily calorie requirement as a half dose of PN via an intravenous central catheter; the third group consisted of controls (n = 14) with full enteral feeding and full enteral fluid intake with no PN and no central venous catheter. At the end of the 10-day study period, the rabbits were subjected to echocardiographic examination and euthanized. Blood and tissue samples were obtained from all groups. DNA was isolated from nucleated blood cells. Tissue samples were examined by both light and electron microscopy, relative telomere length was determined from DNA, and blood samples were analyzed biochemically. RESULTS: At the end of the study, there were no statistically significant differences in weight change between the three groups. Echocardiography revealed minimally impaired diastolic function in the PN + fasting group compared to the other groups. Biochemical and histopathological analyses, relative telomere length determination, and electron micrographs showed significant cardiac damage in the PN + fasting group but not in the PN + oral feeding group or the control group. The blood biochemical analyses showed hyperglycemia and a low insulin level in the PN + fasting group but not in the other two groups. CONCLUSIONS: A combination of PN and fasting may damage the cardiac muscle cells of rabbits via a mechanism involving hyperglycemia and oxidative stress. Additional enteral feeding may protect against the destructive effects of PN on cardiac tissue.


Assuntos
Cardiotoxinas , Coração/fisiopatologia , Miocárdio/patologia , Nutrição Parenteral/efeitos adversos , Animais , Hiperglicemia/etiologia , Insulina/sangue , Coelhos
13.
Gene ; 706: 172-180, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31082499

RESUMO

Molecular mechanisms of aging and longevity are still mostly unknown. Mitochondria play central roles in cellular metabolism and aging. In this study, we identified three deletion mutants of mitochondrial metabolism genes (ppa2∆, dss1∆, and afg3∆) that live longer than wild-type cells. These long-lived cells harbored significantly decreased amount of mitochondrial DNA (mtDNA) and reactive oxygen species (ROS). Compared to the serpentine nature of wild-type mitochondria, a different dynamics and distribution pattern of mitochondria were observed in the mutants. Both young and old long-lived cells produced relatively low but adequate levels of ATP for cellular activities. The status of the retrograde signaling was checked by expression of CIT2 gene and found activated in long-lived mutants. The mutant cells were also profiled for their gene expression patterns, and genes that were differentially regulated were determined. All long-lived cells comprised similar pleiotropic phenotype regarding mitochondrial dynamics and functions. Thus, this study suggests that DSS1, PPA2, and AFG3 genes modulate the lifespan by altering the mitochondrial morphology and functions.


Assuntos
Longevidade/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Envelhecimento , DNA Mitocondrial/metabolismo , Exorribonucleases/genética , Exorribonucleases/metabolismo , Genes Mitocondriais/genética , Genótipo , Proteínas Mitocondriais/genética , Estresse Oxidativo , Fenótipo , Bombas de Próton/genética , Bombas de Próton/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Deleção de Sequência , Transdução de Sinais
14.
J Burn Care Res ; 40(3): 302-311, 2019 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-30805617

RESUMO

BACKGROUND: Burns are a common traumatic injury triggered by local tissue damage and a systemic response. In this study, we evaluated the effects of different burn dressings on telomere kinetics in children with thermal burn injury. METHODS: Sixty children with thermal burn were included in this prospective study. The burn area of the patients included 20 to 50% total body surface area. Three different dressings (hydrofiber with silver [HFAg], poylactic membrane [PLM], and silver sulfadiazine [SSD]) and control groups were created. Telomere length in nucleated blood cells and telomerase expression in the skin tissue were evaluated in control and burn groups. RESULTS: In the whole burn groups, telomere length in blood cells increased. The length of telomeres increased the most in the SSD group. The PLM group is the treatment that increases the number of squamous cell counts in the basal layer and telomerase expression in the skin. In HFAg and SSD groups, the expression of telomerase in the skin is decreased. In the HFAg group, the basal layer in the skin was also reduced in squamous cells. CONCLUSION: In all burn groups, the telomere length of nucleated cells in the blood was higher than in the control group. SSD dressing along with autografting is the treatment method that maximizes telomere length in blood cells. The PLM has the most increased telomerase expression in the skin of burned patients. The PLM application increases the number of cells on both burned and normal skin.


Assuntos
Bandagens , Queimaduras/genética , Queimaduras/terapia , Telomerase/genética , Telômero/genética , Cicatrização/efeitos dos fármacos , Adolescente , Anti-Infecciosos Locais/farmacologia , Biópsia por Agulha , Queimaduras/patologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Lactente , Escala de Gravidade do Ferimento , Masculino , Prognóstico , Estudos Prospectivos , Medição de Risco , Sulfadiazina de Prata/farmacologia , Cicatrização/genética
15.
Eur J Haematol ; 102(2): 123-130, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30300449

RESUMO

OBJECTIVES: To evaluate the long-term efficacy and safety of deferasirox therapy in a large observational cohort of children with transfusion-dependent thalassemia (TDT) and sickle cell anemia (SCA) in Turkey. METHODS: This was a multicenter, prospective cohort study including TDT and SCA patients aged 2-18 years with iron overload (≥100 mL/kg of pRBC or a serum ferritin [SF] level >1000 µg/L) receiving deferasirox. Patients were followed for up to 3 years according to standard practice. RESULTS: A total of 439 patients were evaluated (415 [94.5%] TDT, 143 [32.6%] between 2 and 6 years). Serum ferritin levels consistently and significantly decreased across 3 years of deferasirox therapy from a median of 1775.5 to 1250.5 µg/L (P < 0.001). Serum ferritin decreases were noted in TDT (1804.9 to 1241 µg/L), SCA (1655.5 to 1260 µg/L), and across age groups of 2-6 years (1971.5 to 1499 µg/L), 7-12 years (1688.5 to 1159.8 µg/L), and 13-18 years (1496.5 to 1107 µg/L). Serum ferritin decreases were also noted for all deferasirox dose groups but only significant in patients with doses ≥30 mg/kg/d (n = 120, -579.6 median reduction, P < 0.001). Only 9 (2%) patients had adverse events suspected to be related to deferasirox. Serum creatinine slightly increased but remained within the normal range. CONCLUSIONS: Deferasirox has long-term efficacy and safety in children with TDT and SCA, although higher doses (≥30 mg/kg/d) may be required to achieve iron balance.


Assuntos
Anemia Falciforme/complicações , Deferasirox/uso terapêutico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Talassemia/complicações , Adolescente , Anemia Falciforme/terapia , Biomarcadores , Transfusão de Sangue , Criança , Pré-Escolar , Estudos de Coortes , Deferasirox/administração & dosagem , Deferasirox/efeitos adversos , Feminino , Ferritinas/sangue , Ferritinas/metabolismo , Humanos , Ferro/sangue , Ferro/metabolismo , Quelantes de Ferro/administração & dosagem , Quelantes de Ferro/efeitos adversos , Sobrecarga de Ferro/metabolismo , Masculino , Talassemia/terapia , Resultado do Tratamento , Turquia
16.
Biomed Res Int ; 2018: 2945751, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30410923

RESUMO

PURPOSE: To evaluate the visual, refractive, and topographic outcomes after simultaneous topography-guided transepithelial photorefractive keratectomy (transepithelial TG-PRK) using the Amaris Excimer laser platform and accelerated corneal cross-linking (CXL) in eyes with keratoconus. MATERIALS AND METHODS: Patients with 2 years of follow-up were included in this retrospective case series. Manifest refraction (MR), uncorrected (UDVA) and corrected (CDVA) distance visual acuity, corneal topography, and pachymetry were evaluated at 1, 3, 6, 12, and 24 months after surgery. The root-mean-square of total higher-order aberrations (total HOA-RMS), coma (Coma-RMS), and spherical aberration (SA-RMS) were calculated for 4- and 6-mm diameters. RESULTS: Forty-six eyes of 46 patients were included in the study. Stromal ablation was ≤50 µ in all patients. MR was -3.78±3.26 preoperatively and -1.39±1.82 postoperatively. Significant improvements were seen in the UDVA and Coma-RMS values at 1 month, CDVA and total HOA-RMS values at 3 months, and SA-RMS values at 1 year compared to preoperative levels. UDVA values further improved after 2 years, compared to the 1-year values. No patient lost two or more lines and keratoconus progression was not observed in any patient. CONCLUSION: Simultaneous transepithelial TG-PRK and accelerated CXL resulted in significant gains in CDVA without compromising CXL efficacy.


Assuntos
Substância Própria/cirurgia , Reagentes de Ligações Cruzadas/uso terapêutico , Ceratocone/tratamento farmacológico , Ceratocone/cirurgia , Adolescente , Adulto , Substância Própria/efeitos dos fármacos , Topografia da Córnea/métodos , Células Epiteliais/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Lasers de Excimer , Masculino , Fotoquimioterapia/métodos , Ceratectomia Fotorrefrativa/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Refração Ocular/efeitos dos fármacos , Estudos Retrospectivos , Acuidade Visual/efeitos dos fármacos , Adulto Jovem
17.
Turk J Haematol ; 35(1): 27-34, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28179213

RESUMO

OBJECTIVE: This study aimed to define the status of juvenile myelomonocytic leukemia (JMML) patients in Turkey in terms of time of diagnosis, clinical characteristics, mutational studies, clinical course, and treatment strategies. MATERIALS AND METHODS: Data including clinical and laboratory characteristics and treatment strategies of JMML patients were collected retrospectively from pediatric hematology-oncology centers in Turkey. RESULTS: Sixty-five children with JMML diagnosed between 2002 and 2016 in 18 institutions throughout Turkey were enrolled in the study. The median age at diagnosis was 17 months (min-max: 2-117 months). Splenomegaly was present in 92% of patients at the time of diagnosis. The median white blood cell, monocyte, and platelet counts were 32.9x109/L, 5.4x109/L, and 58.3x109/L, respectively. Monosomy 7 was present in 18% of patients. JMML mutational analysis was performed in 32 of 65 patients (49%) and PTPN11 was the most common mutation. Hematopoietic stem cell transplantation (HSCT) could only be performed in 28 patients (44%), the majority being after the year 2012. The most frequent reason for not performing HSCT was the inability to find a suitable donor. The median time from diagnosis to HSCT was 9 months (min-max: 2-63 months). The 5-year cumulative survival rate was 33% and median estimated survival time was 30±17.4 months (95% CI: 0-64.1) for all patients. Survival time was significantly better in the HSCT group (log-rank p=0.019). Older age at diagnosis (>2 years), platelet count of less than 40x109/L, and PTPN11 mutation were the factors significantly associated with shorter survival time. CONCLUSION: Although there has recently been improvement in terms of definitive diagnosis and HSCT in JMML patients, the overall results are not satisfactory and it is necessary to put more effort into this issue in Turkey.


Assuntos
Leucemia Mielomonocítica Juvenil/epidemiologia , Biópsia , Pré-Escolar , Terapia Combinada , Feminino , Testes Genéticos , Humanos , Lactente , Leucemia Mielomonocítica Juvenil/diagnóstico , Leucemia Mielomonocítica Juvenil/etiologia , Leucemia Mielomonocítica Juvenil/terapia , Masculino , Vigilância em Saúde Pública , Estudos Retrospectivos , Análise de Sobrevida , Avaliação de Sintomas , Turquia/epidemiologia
18.
Indian J Med Paediatr Oncol ; 38(2): 128-132, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28900319

RESUMO

AIM: In recent years, it is believed that Vitamin D may play a protective role in some cancer types. Certain regions of the Vitamin D receptor (VDR) gene may show a genetic difference in structure. The most frequent polymorphisms in this gene are in Taq-1, Fok-1, and Bsm-1 regions. Some adult cancer types are associated with VDR gene polymorphism such as; colorectal carcinoma, breast carcinoma, and prostate carcinoma. Reviewing the medical literature, no such study had been done on children so far. MATERIALS AND METHODS: We investigated the association of the three most common gene polymorphisms (Taq-1, Fok-1, and Bsm-1 regions) in VDR gene in 32 children with brain tumors and forty control healthy volunteers. RESULTS: We could not find any relationship between childhood brain tumors and VDR gene polymorphism in these three regions. CONCLUSION: The present results suggest that the Taq-1, Fok-1, and Bsm-1 polymorphism in the VDR gene and pediatric brain cancers have no association.

19.
Turk J Pediatr ; 58(1): 47-53, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27922236

RESUMO

Chemotherapy induced febrile neutropenia predisposes patients to life threatening infections. We aimed to determine the causative microorganisms, infection focus and antibiotic treatment success in febrile neutropenic children with leukemia. A total of 136 febrile neutropenic episodes in 48 leukemic children were reviewed retrospectively from records. Among 136 febrile neutropenic episodes, 68 (50%) episodes were microbiologically documented. Methicillin sensitive coagulase (-) Staphylococcus aureus were the most common isolates from hemoculture (20.5%). The most frequently documented infection focus was mucositis (31.9%). Ceftazidime plus amikacin was the most commonly used antimicrobial treatment for the empirical therapy (52.9%). The overall response rates were 70.5%, 86.9%, and 66.6% of first line, second line and third line therapies, respectively. The spectrum of isolates among febrile neutropenic children in our hematology clinic appears to be gram positive pathogens which are the most common agents. Therefore the, documentation of the flora in each unit could help to decide appropriate empirical therapy which is life saving.


Assuntos
Antibacterianos/uso terapêutico , Bactérias/isolamento & purificação , Neutropenia Febril/microbiologia , Adolescente , Amicacina/uso terapêutico , Ceftazidima/uso terapêutico , Criança , Pré-Escolar , Quimioterapia Combinada , Neutropenia Febril/tratamento farmacológico , Neutropenia Febril/epidemiologia , Feminino , Humanos , Lactente , Leucemia/complicações , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Turquia/epidemiologia
20.
Pediatr Hematol Oncol ; 33(3): 200-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27057782

RESUMO

The aim of the present study was to determine the diagnostic value of soluble urokinase plasminogen activator receptor (suPAR) in pediatric patients with febrile neutropenia. A prospective case-control study was performed. Patients included 29 children with febrile neutropenia (FN) and 27 control subjects without any infection or immunosuppressive condition. Blood samples were obtained on the day of admission and on the 4th to 7th days of the hospital stay. The median (minimum-maximum) serum levels of suPAR obtained on the first day of the admission were 2.08 (0.93-9.42) and 2.22 (1.08-5.13) ng/mL for the FN group and the control group, respectively. The median serum levels of suPAR in the FN and control groups were not significantly different (P = .053). The mean serum suPAR level was significantly higher in nonsurvivors than in survivors in the FN group (P < .05). In the FN group, the area under the receiver operating characteristics curve (AUCROC) for suPAR was 0.546, but no optimum cutoff value, sensitivity, specificity, negative predictive value (NPV), or positive predictive value (PPV) was obtained. We conclude that suPAR is not useful as a diagnostic biomarker in children with febrile neutropenia; however, persistent high serum suPAR level may predict mortality in FN in children.


Assuntos
Proteína C-Reativa/análise , Calcitonina/sangue , Neutropenia Febril/diagnóstico , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Neutropenia Febril/sangue , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos
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