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1.
Crit Rev Oncol Hematol ; 137: 131-142, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31014509

RESUMO

Cisplatin (CDDP) is a highly effective antineoplastic agent, widely used in the treatment of various malignant tumors. However, its major problems are side effects associated to toxicity. Considerable inter-individual differences have been reported for CDDP-induced toxicity due to genetic and epigenetic factors. Genetic causes are well described; however, epigenetic modifications are not fully addressed. In the last few years, many evidences were found linking microRNA to the development of CDDP-mediated toxicity, particularly nephrotoxicity. In this review, we described how genetic and epigenetic modifications can be important determinants for the development of toxicity in patients treated with CDDP, and how these alterations may be interesting biomarkers for monitoring toxicity induced by CDDP. Considering the validation in different studies, we suggest that miR-34a, -146b, -378a, -192, and -193 represent an attractive study group to evaluate potential biomarkers to detect CDDP-related nephrotoxicity.


Assuntos
Cisplatino/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/genética , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/efeitos adversos , Epigênese Genética , Humanos , MicroRNAs/genética
2.
Int J Clin Pharm ; 41(1): 74-80, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30552622

RESUMO

Background The emergence and rapid spread of multidrug-resistant gram-negative bacteria related to nosocomial infections is a growing worldwide problem, and polymyxins have become important due to the lack of new antibiotics. Objectives To evaluate the outcomes and pharmacoeconomic impact of using colistin and polymyxin B to treat nosocomial infections. Setting Neurosurgical, cardiovascular, or transplantation intensive care unit (ICU) at the Clinical Hospital of the University of Campinas (São Paulo, Brazil). Method A retrospective cohort study was conduct in patients in the ICU. The renal function was determined daily during treatment by measuring the serum creatinine. A cost minimization analysis was performed to compare the relative costs of treatment with colistin and polymyxin B. Main outcomes measure The outcomes were 30-day mortality and frequency and onset of nephrotoxicity after beginning treatment. Results Fifty-one patients treated with colistin and 51 with polymyxin B were included. 30-day mortality was observed in 25.49% and 33.33% of patients treated with colistin and polymyxin B, respectively; Nephrotoxicity was observed in 43.14% and 54.90% of patients in colistin and polymyxin B groups, respectively; and onset time of nephrotoxicity was 9.86 ± 13.22 days for colistin and 10.68 ± 9.93 days for polymyxin B group. Colistin treatment had a lower cost per patient compared to the cost for polymyxin B treatment (USD $13,389.37 vs. USD $13,639.16, respectively). Conclusion We found no difference between 30-day mortality and nephrotoxicity between groups; however, colistin proved to be the best option from a pharmacoeconomic point of view.


Assuntos
Antibacterianos/economia , Colistina/economia , Infecção Hospitalar/economia , Farmacoeconomia , Unidades de Terapia Intensiva/economia , Polimixina B/economia , Adulto , Idoso , Antibacterianos/uso terapêutico , Brasil/epidemiologia , Estudos de Coortes , Colistina/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Custos de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimixina B/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
3.
Pediatr Emerg Care ; 2018 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-30106866

RESUMO

OBJECTIVES: The objectives of this study were to analyze adverse drug events (ADEs) related to admissions to a pediatric emergency unit and to identify the associated risk factors. METHODS: This was a prospective study. Demographic data and details of medications were collected for each patient admitted. Case studies were performed by clinical pharmacists and the clinical team to discuss whether the admission was due to an ADE and to characterize the ADE. Multivariate logistic regression was used for statistical analysis. RESULTS: In total, 1708 pediatric patients were included in this study. Adverse drug events were the cause of hospital admission in 12.3% of the studied population. The majority of patients presenting with an ADE were in the age group of 0 to 5 years (61.6%), had a mean ± SD age of 4.9 ± 3.9 years, were female (51.2%), were Caucasian (72.0%), and had infectious disorders (49.3%). High frequencies of medication errors (68.8%), use of drugs to treat respiratory disorders (27.7%), and ADEs of mild severity (75.3%) were reported. The risk of being admitted to the pediatric emergency unit for any ADE increased in cases of neurological (odds ratio [OR], 4.63; 95% confidence interval [CI], 2.38-8.99), dermatological (OR, 3.16; 95% CI, 1.93-5.18), and respiratory (OR, 3.02; 95% CI, 1.89-4.83) disorders. CONCLUSIONS: A high frequency of ADE-related admissions to the pediatric emergency unit was observed. The risk of being admitted to the pediatric emergency unit for any ADE increased in cases of neurological, dermatological, and respiratory disorders. Clinical pharmacists play an important role in the identification of ADEs and the education of child caregivers and health care providers concerning pediatric medication.

4.
Oncotarget ; 9(51): 29538-29547, 2018 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-30038702

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is treated with cisplatin (CDDP) and radiotherapy (RT), and distinct results are observed among patients with similar clinicopathological aspects. This prospective study aimed to investigate whether MLH1 c.-93G>A (rs1800734), MSH2 c.211+9C>G (rs2303426), MSH3 c.3133G>A (rs26279), EXO1 c.1765G>A (rs1047840), and EXO1 c.2270C>T (rs9350) single nucleotide polymorphisms (SNPs) of the mismatch repair (MMR) pathway change side effects and response rate of 90 HNSCC patients treated with CDDP and RT. DNA from peripheral blood was analyzed by PCR-based methods to obtain genotypes. It was observed 4.27-fold and 4.69-fold increased risks of presenting pronounced nephrotoxicity with treatment in patients with MSH3 GG and EXO1 rs9350 CC genotypes compared with patients with GA or AA and CT or TT genotypes, respectively. MSH3 GG or GA and GT haplotype of EXO1 rs1047840 and rs9350 SNPs conferred to patients 10.29 and 4.00 more chances of presenting pronounced ototoxicity after treatment than MSH3 AA genotype and other EXO1 haplotypes, respectively. Patients with EXO1 rs1047840 GA or AA genotype and AC haplotype of EXO1 rs1047840 and rs9350 SNPs had both 9.55-fold increased risks of achieving partial response or stable disease instead of complete remission after treatment than patients with EXO1 GG genotype and other EXO1 haplotypes, respectively. For the first time, our data show preliminary indication that inherited alterations of DNA MMR pathway, related to MSH3 rs26279, EXO1 rs1047840 and EXO1 rs9350 SNPs, modify toxicity and response to chemoradiation in HNSCC, and may contribute to future personalized treatment of patients.

6.
BMC Cancer ; 17(1): 831, 2017 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-29212535

RESUMO

BACKGROUND: Leukocytoclastic vasculitis is typically mediated by deposition of immune complexes and is related to many causes, including medication. To the best of our knowledge, leukocytoclastic vasculitis related to cisplatin has not yet been described in the scientific literature. CASE PRESENTATION: We report a rare case of leukocytoclastic vasculitis after the first cycle of high-dose cisplatin chemotherapy in a patient with larynx carcinoma. A 48-year-old Caucasian man with larynx carcinoma received a high-dose of cisplatin monochemotherapy (100 mg/m2 every 21 days), along with 70 Gy of radiotherapy divided into 35 sessions, as a therapeutic schedule. Twelve days after the first chemotherapy administration and after 8 sessions of radiotherapy (total of 16 Gy), the patient presented with acute onset of palpable purpura in the lower limbs. The patient was hospitalized for 10 days, and during this period, he underwent several examinations to rule out infectious, autoimmune, and neoplastic disorders. A skin biopsy showed leukocytoclastic vasculitis with a positive pattern for IgM and C3, as detected through direct immunofluorescence. Twenty-five days after cisplatin administration, the chemotherapy regimen was changed to carboplatin AUC 5, and the episodes of purpura ceased, reinforcing the hypothesis of an adverse reaction to cisplatin. CONCLUSIONS: Cisplatin can induce leukocytoclastic vasculitis and clinicians should be aware of this potential effect for better case management and diagnosis.


Assuntos
Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Neoplasias Laríngeas/tratamento farmacológico , Vasculite Leucocitoclástica Cutânea/induzido quimicamente , Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Humanos , Neoplasias Laríngeas/complicações , Neoplasias Laríngeas/radioterapia , Perna (Membro)/irrigação sanguínea , Perna (Membro)/patologia , Masculino , Pessoa de Meia-Idade , Pele/irrigação sanguínea , Pele/patologia , Vasculite Leucocitoclástica Cutânea/complicações , Vasculite Leucocitoclástica Cutânea/patologia
7.
Basic Clin Pharmacol Toxicol ; 121(6): 520-525, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28686330

RESUMO

Cisplatin (CDDP) chemotherapy associated with radiation (RT) has been used in advanced head and neck squamous cell carcinoma (HNSCC) patients, and vomiting is a common side effect during treatment. This prospective study aimed to identify the roles of GSTM1 and GSTT1 (presents or nulls), GSTP1 c.313A>G, XPC c.2815A>C, XPD c.934G>A and c.2251A>C, XPF c.2505T>C, ERCC1 c.354C>T, MLH1 c.-93G>A, MSH2 c.211 + 9C>G, MSH3 c.3133G>A, EXO1 c.1765G>A, TP53 c.215G>C, CASP3 c.-1191A>G and c.-1168G>T, CASP9 c.-1339A>G, CASP8 c.-937_-932delAGTAAG, FAS c.-1378G>A and c.-671A>G, and FASL c.-157-687C>T single nucleotide polymorphisms, involved in CDDP metabolism, in vomiting severity in 88 HNSCC patients treated with CDDP and RT. Ondansetron and dexamethasone were administered as anti-emetic therapy. Patients with GSTP1 c.313AG or GG genotype alone and combined with XPD c.934GA or AA, XPF c.2505TC or CC, and CASP9 c.-1339AG or GG genotypes had 4.28, 5.00, 5.45 and 5.38 more chances of presenting moderate/severe vomiting than patients with others genotypes. Our data suggest, for the first time, that inherited abnormality in apoptosis pathway alone or combined with inherited abnormalities in DNA repair pathway, is capable of modulating emesis in HNSCC patients under CDDP chemoradiation and may be used for selecting patients who should receive pre-emptive anti-emetic therapy.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/efeitos adversos , Cisplatino/efeitos adversos , Predisposição Genética para Doença/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Vômito/induzido quimicamente , Vômito/genética , Adulto , Idoso , Antieméticos/uso terapêutico , Antineoplásicos/farmacocinética , Carcinoma de Células Escamosas/complicações , Cisplatino/farmacocinética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Neoplasias de Cabeça e Pescoço/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço , Vômito/tratamento farmacológico
8.
Rev Bras Ginecol Obstet ; 39(6): 258-264, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28571055

RESUMO

Introduction In the pregnancy-puerperal cycle, women may develop complications that require admission to the Intensive Care Unit (ICU). Thus, special attention to pharmacotherapy is necessary, particularly to potential drug interactions (PDIs) and to the effect of the drugs on the fetus and newborn. Objective The aim of this study was to determine the profile of PDIs and the potential risk of drugs used during pregnancy and breastfeeding among patients admitted to the ICU. Methods We conducted an observational, cross-sectional and prospective study, including pregnant and breastfeeding women admitted to the ICU at the Women's Hospital of a university in the city of Campinas, Brazil, for one year. Online databases were used to identify and classify the PDIs and the potential risk of the drugs used during pregnancy and breastfeeding. Results We evaluated 305 prescriptions of 58 women, 31 pregnant and 27 breastfeeding, and 284 (91%) prescriptions presented PDIs. A total of 175 different combinations of PDIs were identified in the prescriptions, and adverse effects caused by the simultaneous use of drugs were not actually observed in the clinical practice. A total of 26 (1.4%) PDIs were classified as contraindicated. We identified 15 (13.8%) drugs prescribed with risk D, and 2 (1.8%) with risk X for pregnant women, as well as 4 (4.9%) drugs prescribed with high risk for breastfeeding women. Conclusions This study demonstrates that there is a high incidence of PDIs in prescriptions. Most drugs used by pregnant and breastfeeding women at the ICU did not present serious risks to their fetus and newborns, but sometimes drugs with risk D or X are necessary in the course of the treatment.


Assuntos
Aleitamento Materno , Interações de Medicamentos , Feto/efeitos dos fármacos , Adulto , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Unidades de Terapia Intensiva , Pessoa de Meia-Idade , Período Pós-Parto , Gravidez , Estudos Prospectivos , Adulto Jovem
9.
Cancer Chemother Pharmacol ; 80(2): 223-233, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28612092

RESUMO

PURPOSE: The aim of this study is to evaluate the relationship between the CYP450 enzyme family and cisplatin toxicity. METHODS: This article examined a collection of studies suggesting that CYP450 enzymes may influence cisplatin toxicity. We performed a narrative mini-review. RESULTS: The studies review showed that CYP450 enzymes have an important role in drug-induced hepatotoxicity and nephrotoxicity, mainly CYP2E1 and CYP4A11. The studies also suggested that the cisplatin and CYP2E1 interaction leads to the generation of reactive oxygen species (ROS) and other oxidants resulting in renal injury; and that ROS generated by both the use of cisplatin and by the CYP2E1 increases tissue damage, induces apoptosis, and causes liver failure. CONCLUSIONS: We observed that there is an important relationship between CYP450 and cisplatin, involving increased toxicity. However, the possible mechanisms described for the involvement of CYP450 enzymes in nephrotoxicity and hepatotoxicity induced by cisplatin need to be confirmed by further studies. Therefore, there is a need for a deeper investigation focusing on cisplatin toxicity mediated by CYP450 enzymes, which would undoubtedly contribute to a better understanding of the mechanisms that have been implicated so far.


Assuntos
Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Sistema Enzimático do Citocromo P-450/metabolismo , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Citocromo P-450 CYP2E1/metabolismo , Citocromo P-450 CYP4A/metabolismo , Humanos , Nefropatias/induzido quimicamente , Nefropatias/enzimologia , Espécies Reativas de Oxigênio/metabolismo
10.
Rev. bras. ginecol. obstet ; 39(6): 258-264, June 2017. tab
Artigo em Inglês | LILACS-Express | ID: biblio-898867

RESUMO

Abstract Introduction In the pregnancy-puerperal cycle, women may develop complications that require admission to the Intensive Care Unit (ICU). Thus, special attention to pharmacotherapy is necessary, particularly to potential drug interactions (PDIs) and to the effect of the drugs on the fetus and newborn. Objective The aim of this study was to determine the profile of PDIs and the potential risk of drugs used during pregnancy and breastfeeding among patients admitted to the ICU. Methods We conducted an observational, cross-sectional and prospective study, including pregnant and breastfeeding women admitted to the ICU at the Women's Hospital of a university in the city of Campinas, Brazil, for one year. Online databases were used to identify and classify the PDIs and the potential risk of the drugs used during pregnancy and breastfeeding. Results We evaluated 305 prescriptions of 58 women, 31 pregnant and 27 breastfeeding, and 284 (91%) prescriptions presented PDIs. A total of 175 different combinations of PDIs were identified in the prescriptions, and adverse effects caused by the simultaneous use of drugs were not actually observed in the clinical practice. A total of 26 (1.4%) PDIs were classified as contraindicated. We identified 15 (13.8%) drugs prescribed with risk D, and 2 (1.8%) with risk X for pregnant women, as well as 4 (4.9%) drugs prescribed with high risk for breastfeeding women. Conclusions This study demonstrates that there is a high incidence of PDIs in prescriptions. Most drugs used by pregnant and breastfeeding women at the ICU did not present serious risks to their fetus and newborns, but sometimes drugs with risk D or X are necessary in the course of the treatment.


Resumo Introdução No ciclo gravídico-puerperal, as mulheres podem desenvolver complicações que necessitam de internação na Unidade de Terapia Intensiva (UTI). Assim, é necessária uma atenção especial à farmacoterapia, particularmente às interações medicamentosas potenciais (IMPs) e ao risco dos medicamentos para o feto e o recémnascido. Objetivo Determinar o perfil das IMPs e o risco potencial dos medicamentos utilizados durante a gravidez e a amamentação entre as mulheres internadas em UTI. Métodos Foi realizado um corte transversal e prospectivo, observacional, incluindo mulheres grávidas e lactantes internadas na UTI do Hospital da Mulher de uma universidade de Campinas durante um ano. Bases de dados online foram usadas para identificar e classificar as IMPs e o potencial risco de uso de medicamentos durante a gravidez e a amamentação. Resultados Foram avaliadas 305 prescrições de 58 mulheres, 31 grávidas e 27 lactantes, e 284 (91%) prescrições apresentaram IMPs, sendo que 175 combinações diferentes de IMPs foram identificadas nas prescrições, e não foram observados efeitos nocivos pelo uso concomitante dos medicamentos na prática clínica. Um total de 26 (1,4%) IMPs foram classificadas como contraindicadas. Foram identificados 15 (13,8%) medicamentos prescritos com risco D, e 2 (1,8%) com risco X para mulheres grávidas, e foram identificados 4 (4,9%) medicamentos prescritos como de alto risco para as mulheres que estavam amamentando. Conclusões Este estudo demonstra que há uma alta incidência de IMPs nas prescrições. A maioria dos medicamentos utilizados por mulheres grávidas e lactantes em UTI não apresentou sérios riscos para o feto e o recém-nascido, mas às vezes são necessários medicamentos categorizados como risco D ou X.

11.
Daru ; 25(1): 12, 2017 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-28438219

RESUMO

BACKGROUND: Cisplatin is a high-potency anticancer agent; however, it causes significant adverse drug reactions (ADRs). Potential pharmacokinetic markers must be studied to predict or prevent cisplatin-induced ADRs and achieve better prognosis. This study was designed to investigate the relationship between ADRs and kinetics of cisplatin excretion in the urine of patients undergoing high-dose cisplatin chemotherapy and radiotherapy for head and neck cancer. METHODS: Outpatients with head and neck cancer received a first cycle of high-dose cisplatin chemotherapy (80-100 mg/m2) concurrent to radiotherapy. ADRs (haematological, renal, and gastrointestinal reactions) were classified based on severity by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 4, grade 0-4). The kinetics of cisplatin excretion in urine was evaluated by high-performance liquid chromatography over three time periods: 0-12, 12-24, and 24-48 h after the administration of cisplatin. Spearman Correlation test and regression analysis were performed to assess the relationship between ADRs and cisplatin excretion in the urine. RESULTS: In total, 59 patients with a mean age of 55.6 ± 9.4 years were analysed; most patients were male (86.4%), white (79.7%), and with pharyngeal tumours in advanced stages (66.1%). The most frequently observed ADRs were anaemia (81.4%), lymphopenia (78%), and nausea (64.4%); mostly grades 1 and 2 of toxicity. The mean cisplatin excretion was 70.3 ± 64.4, 7.3 ± 6.3, and 5 ± 4 µg/mg creatinine at 0-12, 12-24, and 24-48 h, respectively. Statistical analysis showed that the amount of cisplatin excreted did not influence the severity of ADRs. CONCLUSIONS: The most frequent ADRs were anaemia, lymphopenia, and nausea. Grades 1 and 2 were the severities for most ADRs. The period over which the highest cisplatin excretion observed was 0-12 h after chemotherapy, and cisplatin excretion could not predict toxicity.


Assuntos
Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Neoplasias de Cabeça e Pescoço/terapia , Anemia/induzido quimicamente , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Antineoplásicos/urina , Quimiorradioterapia/métodos , Cisplatino/farmacocinética , Cisplatino/uso terapêutico , Cisplatino/urina , Feminino , Humanos , Linfopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neoplasias Faríngeas/terapia , Estudos Prospectivos
12.
Oncotarget ; 8(10): 16190-16201, 2017 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-26918827

RESUMO

This study aimed to investigate the associations of XPC c.2815A>C, XPD c.934G>A and c.2251A>C, XPF c.2505T>C and ERCC1 c.354C>T single nucleotide polymorphisms (SNPs) of nucleotide excision repair pathway in outcome of head and neck squamous cell carcinoma (HNSCC) patients treated with cisplatin (CDDP) chemoradiation. Patients with XPC c.2815AC or CC and XPD c.934GA or AA genotypes had 0.20 and 0.38 less chances of presenting moderate/severe ototoxicity and nausea, respectively. Patients with XPD c.934AA and c.2251AC or CC genotypes had 8.64, 12.29 and 3.55 more chances of achieving complete response (CR), consistent ototoxicity and nephrotoxicity, respectively. AA haplotype of XPD and ACT haplotype of XPD and ERCC1 SNPs were associated with 9.30 and 3.41 more chances of achieving CR and consistent nephrotoxicity, respectively. At 24 months of follow-up, patients with XPD c.934AA genotype presented lower progression-free survival and overall survival in Kaplan-Meier estimates, and differences between groups remained the same in univariate Cox analysis. Patients with XPD c.934AA genotype had 2.13 and 2.04 more risks of presenting tumor progression and death than others in multivariate Cox analysis. Our data present preliminary evidence that XPC c.2815A>C, XPD c.934G>A and c.2251A>C, and ERCC1 c.354C>T SNPs alter outcome of HNSCC patients treated with CDDP chemoradiation.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/uso terapêutico , Reparo do DNA , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Proteína Grupo D do Xeroderma Pigmentoso/genética , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/genética , Cisplatino/efeitos adversos , Feminino , Seguimentos , Genótipo , Haplótipos , Neoplasias de Cabeça e Pescoço/genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Náusea/induzido quimicamente , Neutropenia/induzido quimicamente , /estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Transdução de Sinais/genética , Vômito/induzido quimicamente
13.
Biomed Res Int ; 2015: 963569, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26509174

RESUMO

BACKGROUND: Phase I of this study was aimed at comparing the profiles of oxidative stress biomarkers in patients with history of nonmelanoma skin cancer (NMSC), previously treated with surgery, to the healthy subjects. Phase II aimed to evaluate the effects of supplementary antioxidant therapy on the levels of biomarkers in the case group. MATERIALS AND METHODS: In Phase I, oxidative stress biomarkers were measured in blood samples obtained from 24 healthy subjects and 60 patients with history of NMSC previously treated with surgery. In Phase II, the 60 patients with history of NMSC were randomized into two subgroups, one receiving placebo (n = 34) and the other (n = 26) receiving vitamin C, vitamin E, and zinc supplementation for 8 weeks, followed by reevaluation of biomarkers. RESULTS: In Phase I, patients with history of NMSC showed increased plasma concentrations of all biomarkers, but only 15-F2t-isoprostane was significantly higher than in the healthy subjects. Risk of NMSC increased by 4% for each additional 1 pg/mL increase in 15-F2t-isoprostane. In Phase II, supplementation did not significantly reduce levels of oxidative stress biomarkers. CONCLUSION: Patients with history of NMSC had significantly high 15-F2t-isoprostane plasma levels; supplementation did not result in significant reduction of oxidative stress biomarkers. This trial was registered with ClinicalTrials.gov (ID NCT02248584).


Assuntos
Biomarcadores Tumorais/sangue , Isoprostanos/sangue , Estresse Oxidativo/efeitos dos fármacos , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Antioxidantes/administração & dosagem , Ácido Ascórbico/administração & dosagem , Suplementos Nutricionais , Dinoprosta/análogos & derivados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/patologia , Vitamina E/administração & dosagem , Zinco/administração & dosagem
14.
South Med J ; 108(6): 343-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26079459

RESUMO

OBJECTIVES: The aim of this study was to evaluate the quality of life (QOL) of patients with squamous cell carcinoma of the head and neck before and during treatment with high-dose cisplatin and radiotherapy. METHODS: This was an observational and longitudinal prospective study conducted from June 2011 to March 2013 at the clinical oncology ambulatory unit of a public teaching hospital in São Paulo, Brazil. The University of Washington Quality of Life Questionnaire was used to measure the QOL of patients before and after each chemotherapy cycle with high-dose cisplatin (80-100 mg/m(2), three cycles) and radiotherapy (2 Gy, 5 days/week for 7 weeks). Data were analyzed using Student t tests, and P < 0.05 was considered statistically significant. RESULTS: Thirty-two patients completed the three cycles of treatment. The study population consisted primarily of white men with a mean age older than 50 years, who had a partner, a low education level, and who were heavy smokers and drinkers, Karnofsky Performance Status of 90% to 100%, pharynx tumors, and stage IV cancer, classified as T4 and N2 stages; the minority of them required interventions such as a feeding tube and tracheostomy. We observed a reduction in QOL after treatment initiation; this reduction was significant after the second chemotherapy cycle and the sixth week of radiotherapy. The abilities to taste, swallow, salivate, and participate in activities and recreation were affected significantly. We also observed a significant improvement in pain and anxiety resulting from the chemoradiation. CONCLUSIONS: Healthcare providers need to be aware of the affected domains to provide improved QOL, well-being, and security to cancer patients who are receiving this type of treatment.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Cisplatino/administração & dosagem , Neoplasias de Cabeça e Pescoço/terapia , Qualidade de Vida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/fisiopatologia , Feminino , Neoplasias de Cabeça e Pescoço/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Faríngeas/terapia , Estudos Prospectivos , Dosagem Radioterapêutica , Sensação , Carcinoma de Células Escamosas de Cabeça e Pescoço , Adulto Jovem
15.
Contemp Oncol (Pozn) ; 19(2): 148-53, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26034394

RESUMO

AIM OF THE STUDY: To identify predictors of quality of life (QOL) in head and neck cancer patients prior to cisplatin chemotherapy and radiotherapy treatment. MATERIAL AND METHODS: A cross-sectional study at a Clinical Oncology department of a teaching hospital in the state of São Paulo, Brazil, from September 2011 to October 2012 was performed. QOL was assessed using the University of Washington QOL Questionnaire. Demographic and clinical characteristics were obtained through interviews with patients and collected from medical records. Multivariate linear regression was used to determine the association between QOL scores and patient-related factors. RESULTS: We studied 48 head and neck cancer patients, who were mostly white (77.1%), males (83.3%), with pharyngeal cancers (66.7%), cancers with stage T4 (45.8%) and N1 (31.2%) tumours, and classified with a Karnofsky Performance Status (KPS) of 90% (37.5%). Patients had excellent scores for saliva (96.2 ±13.5) and shoulder (93.6 ±17.9), with pain and anxiety being the most affected domains (59.6 ±32.4 and 57.5 ±39.2, respectively). A significant relationship of KPS and T stage with overall QOL score was noted. The population with lowest overall QOL score was those who had low KPS scores and T4 tumours. CONCLUSIONS: Head and neck cancer patients prior to cisplatin chemotherapy and radiotherapy treatment, with a low KPS and staged as T4 tumours, have worse overall QOL, and special attention should be given to these patients.

16.
Saudi Pharm J ; 23(2): 130-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25972731

RESUMO

OBJECTIVES: The aim of this study was to determine the frequency and profile of spontaneous reports of Adverse Drug Reactions (ADRs) and quality deviations in a Brazilian teaching hospital and propose a consistent classification to study quality deviations. METHODS: This is a descriptive and retrospective study involving the analysis of spontaneous reports of ADRs and quality deviations in 2010. ADRs were classified according to the reaction mechanism, severity, and causality. The drugs were classified according to their therapeutic classes and symptoms according to the affected organ. The quality deviations were classified according to the type of deviation and type of medicine available in the Brazilian market. RESULTS: A total of 68 forms were examined; ADRs accounted for 39.7% of the notifications, while quality deviations accounted for 60.3%. ADRs occurred more frequently in men (51.9%) and adults (63.0%). The skin (28.0%) was the most affected organ, while anti-infectives (40.7%) were the therapeutic class that caused the most ADRs. The most common ADRs were type B (74.0%), moderates (37.0%), and probables (55.6%). In relation to quality deviations, the most frequent notifications were breaks, splits and leaks (20.9%) and related to generic drugs (43.9%). CONCLUSION: The classification system to study quality deviations was clear and consistent. This study demonstrated that practices and public policies related to more effective pharmacovigilance need to be implemented so that the number of spontaneous reports increases.

17.
Medicine (Baltimore) ; 94(16): e578, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25906090

RESUMO

UNLABELLED: Cisplatin (CDDP) plus radiotherapy (RT) has been used to treat advanced laryngeal squamous cell carcinoma (LSCC) patients. Single nucleotide polymorphisms (SNPs) may be responsible for differences in chemo/radiosensitivity and side effects in those patients. We reported an advanced LSCC patient, who obtained durable complete response and unexpected pronounced toxicity during CDDP and RT, possibly due to SNPs in genes that modulate the effects of this therapeutic modality. CASE PRESENTATION: A 30-year-old man with advanced LSCC obtained durable complete response and severe alopecia and pancytopenia after standard and reduced doses of CDDP and RT. Analyses of SNPs revealed that the patient presented GSTT1 deletion, variant MSH3 1045ThrThr, wild GSTP1 105IleIle, and wild BAX -248GG genotypes, which were previously described in association with abnormal detoxification, DNA repair, and damaged cell apoptosis, respectively. Seven other advanced LSCC patients with GSTT1 gene, MSH3 AlaAla or AlaThr, GSTP1 IleVal or ValVal, and BAX GA or AA genotypes served as controls of the study. Only 1 control presented complete response; the other 6 controls obtained partial response of short duration. Four and 3 controls presented grade 1 or 2 and grade 3 anemia or leukopenia during treatment, respectively. The CDDP level in urine collected after CDDP infusion in the reported patient was lower than the median value obtained in controls, suggesting a higher amount of intracellular CDDP in the reported case.The data suggest, for the first time, that inherited abnormalities in intracellular detoxification of CDDP, DNA repair of lesions induced by CDDP and RT, and damaged cell apoptosis may alter treatment response and toxicity in LSCC, but should be confirmed by large pharmacogenomic studies.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Cisplatino/uso terapêutico , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/terapia , Adulto , Quimiorradioterapia , Cisplatino/efeitos adversos , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Indução de Remissão , Carcinoma de Células Escamosas de Cabeça e Pescoço , Proteína X Associada a bcl-2/genética
18.
Daru ; 23: 13, 2015 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-25889580

RESUMO

BACKGROUND: Studies have shown that pharmaceutical care can result in favorable clinical outcomes in human immunodeficiency virus (HIV)-infected patients, however, few studies have assessed the economic impact. The objective of this study was to evaluate the clinical and economic impact of pharmaceutical care of HIV-infected patients. METHODS: A controlled ambispective study was conducted in Brazil from January 2009 to June 2012. Patients were allocated to either intervention or control group. The control group was followed according to standard care while the intervention group was also followed by a pharmacist at each physician appointment for one year. Effectiveness outcomes included CD4+ count, viral load, absence of co-infections and optimal immune response, and economic outcomes included expenses of physician and pharmaceutical appointments, laboratory tests, procedures, and hospitalizations, at six months and one year. RESULTS: Intervention and control groups included 51 patients each. We observed significant decreases in total pharmacotherapy problems during the study. At six months, the intervention group contained higher percentages of patients without co-infections and of patients with CD4+ >500 cells/mm(3). None of the differences between intervention and control group considering clinical outcomes and costs were statistically significant. However, at one year, the intervention group showed higher percentage of better clinical outcomes and generated lower spending (not to procedures). An additional health care system daily investment of US$1.45, 1.09, 2.13, 4.35, 1.09, and 0.87 would be required for each additional outcome of viral load <50 copies/ml, absence of co-infection, CD4+ >200, 350, and 500 cells/mm(3), and optimal immune response, respectively. CONCLUSION: This work demonstrated that pharmaceutical care of HIV-infected patients, for a one-year period, was able to decrease the number of pharmacotherapy problems. However, the clinical outcomes and the costs did not have statistical difference but showed higher percentage of better clinical outcomes and lower costs for some items.


Assuntos
Análise Custo-Benefício/métodos , Infecções por HIV/economia , Assistência Farmacêutica/economia , Adulto , Brasil , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
19.
Nutr. hosp ; 31(4): 1682-1688, abr. 2015. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-135074

RESUMO

The non-melanoma skin cancer is the most common cancer and accounts for more than half of the diagnoses of cancer, and basal cell carcinoma (BCC), the most frequent cutaneous neoplasm, corresponding to 70-80% of cutaneous tumors. Oxidative stress is an important trigger for skin carcinogenesis. Thus, it is important to evaluate oxidative stress, in order to discern effective therapeutic strategies able to stop it or attenuate it, thereby prevent the installation of non-melanoma skin cancer. Cross-sectional study with controls, involving 84 individuals of both sexes aged between 38-84 years, divided into two groups: control group of healthy people(n = 24) and the case group included individuals who presented non-melanoma skin and they have undergoing surgery (n = 60). The blood samples of the individuals were obtained for evaluation of biomarkers of oxidative stress (F2-isoprostane, nitrite, thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity). The usual dietary intake and nutritional status of the subjects were evaluated. The significance level for this study was 5%. Patients in the case group had higher serum concentrations of biomarkers of oxidative stress, F2-isoprostane concentrations were significantly higher compared to controls. The results showed high rates of overweight and obesity in the case and control groups. The dietary concentrations of antioxidant minerals zinc, copper and selenium in the case group were significantly lower compared to controls. The correlation between markers of oxidative stress and dietary concentrations of antioxidant nutrients showed the influence of food intake of vitamins A and E in reducing oxidative stress, since these nutrients behave as important antioxidants, acting as sweepers of RL, by removing of the body the negative effects on the redox balance of the skin. We emphasize the importance of adopting healthy eating habits that optimize the consumption of antioxidant nutrients as a strategy to prevent oxidative damage to the skin (AU)


El cáncer de piel no melanoma es el cáncer más común y representa más de la mitad de los diagnósticos de cáncer, y el carcinoma de células basales (BCC), la neoplasia cutánea más frecuente, representando el 70-80% de los tumores cutáneos. El estrés oxidativo es un disparador importante en la carcinogénesis de la piel. Por lo tanto, es importante para evaluar el estrés oxidativo, con el fin de prever y estrategias terapéuticas eficaces capaces de detener o mitigar ella, para evitar de este modo la instalación de cáncer de piel no melanoma. Estudio transversal con los controles, con la participación de 84 sujetos de ambos sexos con edades comprendidas entre 38 a 84 años, divididos en dos grupos: grupo control de sujetos sanos (n =24) personas y el grupo de casos incluyeron los individuos que presentaron para el cáncer de piel no melanoma tiene someterse a la cirugía (n = 60). Las muestras de sangre de los sujetos fueron obtenidos para la evaluación de los biomarcadores de estrés oxidativo (F2-isoprostano, nitritos, sustancias reactivas al ácido tiobarbitúrico (TBARS) y capacidad antioxidante total). Se evaluó la ingesta dietética habitual y el estado nutricional de los sujetos. El nivel de significación para este estudio fue de 5%. Los pacientes en el grupo de casos tenían mayores concentraciones séricas de biomarcadores de estrés oxidativo, las concentraciones de F2-isoprostano fueron significativamente mayor en comparación con los controles. Los resultados mostraron altas tasas de sobrepeso y obesidad en los grupos de casos y controles. Las concentraciones dietéticas de antioxidante minerales de zinc, cobre y selenio en el grupo de casos fueron significativamente más bajos en comparación con los controles. La correlación entre los marcadores de estrés oxidativo y las concentraciones dietéticas de nutrientes antioxidantes destacó la influencia de la ingesta de alimentos de vitaminas A y E en la reducción del estrés oxidativo, ya que estos nutrientes se comportan como antioxidantes importantes, actuando como barrenderos RL, el cuerpo se deshaga de estos efectos negativos sobre el equilibrio redox de la piel. Hacemos hincapié en la importancia de adoptar hábitos de alimentación saludables que optimizan el consumo de nutrientes antioxidantes como estrategia para prevenir el daño oxidativo de la piel (AU)


Assuntos
Humanos , Neoplasias Cutâneas/prevenção & controle , Elementos de Resposta Antioxidante/fisiologia , Nutrientes/análise , Antioxidantes/farmacocinética , Estresse Oxidativo/fisiologia , Biomarcadores Tumorais/análise , F2-Isoprostanos/análise
20.
Nutr Hosp ; 31(4): 1682-8, 2015 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-25795958

RESUMO

The non-melanoma skin cancer is the most common cancer and accounts for more than half of the diagnoses of cancer, and basal cell carcinoma (BCC), the most frequent cutaneous neoplasm, corresponding to 70-80% of cutaneous tumors. Oxidative stress is an important trigger for skin carcinogenesis. Thus, it is important to evaluate oxidative stress, in order to discern effective therapeutic strategies able to stop it or attenuate it, thereby prevent the installation of non-melanoma skin cancer. Cross-sectional study with controls, involving 84 individuals of both sexes aged between 38-84 years, divided into two groups: control group of healthy people(n = 24) and the case group included individuals who presented non-melanoma skin and they have undergoing surgery (n = 60). The blood samples of the individuals were obtained for evaluation of biomarkers of oxidative stress (F2-isoprostane, nitrite, thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity). The usual dietary intake and nutritional status of the subjects were evaluated. The significance level for this study was 5%. Patients in the case group had higher serum concentrations of biomarkers of oxidative stress, F2-isoprostane concentrations were significantly higher compared to controls. The results showed high rates of overweight and obesity in the case and control groups. The dietary concentrations of antioxidant minerals zinc, copper and selenium in the case group were significantly lower compared to controls. The correlation between markers of oxidative stress and dietary concentrations of antioxidant nutrients showed the influence of food intake of vitamins A and E in reducing oxidative stress, since these nutrients behave as important antioxidants, acting as sweepers of RL, by removing of the body the negative effects on the redox balance of the skin. We emphasize the importance of adopting healthy eating habits that optimize the consumption of antioxidant nutrients as a strategy to prevent oxidative damage to the skin.


Assuntos
Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Neoplasias Cutâneas/metabolismo , Adulto , Idoso , Biomarcadores/análise , Estudos Transversais , Comportamento Alimentar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional
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