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1.
J Anaesthesiol Clin Pharmacol ; 40(1): 82-89, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38666154

RESUMO

Background and Aims: Many strategies are available to prevent spinal-induced hypotension in cesarean section, especially the use of a low dose of spinal anesthesia combined with adjuvants. This study investigated the effect of adding either dexmedetomidine or dexamethasone to the intrathecal bupivacaine-fentanyl mixture on the postoperative analgesia duration, after elective cesarean section. Material and Methods: This prospective, randomized, double-blind study was conducted on 90 full-term parturients undergoing elective cesarean section, who were randomly distributed into three groups. They all received spinal anesthesia with the bupivacaine-fentanyl mixture (2.5 ml), in addition to 0.5 ml normal saline (control group), 5 µg dexmedetomidine dissolved in 0.5 ml normal saline (dexmedetomidine group), or 2 mg dexamethasone (dexamethasone group). The time to the first request of morphine rescue analgesia was recorded, in addition to the total dose of morphine consumed in the first 24 h after surgery, the postoperative numerical rating score (NRS), and maternal and fetal outcomes. Results: As compared to the control group and the dexamethasone group, the use of dexmedetomidine as an additive to the bupivacaine-fentanyl mixture significantly prolonged the time to the first request of rescue analgesia, decreased postoperative morphine consumption, and decreased the pain score 4 and 6 h after surgery. There was an insignificant difference between the control and dexamethasone groups. Conclusion: The use of dexmedetomidine as an additive to bupivacaine-fentanyl mixture in spinal anesthesia for cesarean section prolonged the postoperative analgesia and decreased the postoperative opioid consumption in comparison to the addition of dexamethasone or normal saline.

2.
Eur J Clin Pharmacol ; 79(2): 299-309, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36562831

RESUMO

INTRODUCTION: Metformin may provide a therapeutic benefit in different types of malignancy. PURPOSE: We aimed at evaluating the effect of metformin as an adjuvant therapy to letrozole on estradiol and other biomarkers involved in the pathogenesis of breast cancer in overweight and obese postmenopausal women. METHODS: Seventy-five postmenopausal stages II-III breast cancer female patients were assessed for eligibility in an open-labeled parallel pilot study. Forty-five patients met the inclusion criteria and were assigned into three arms: the lean arm (n = 15) women who received letrozole 2.5 mg/day, the control arm (n = 15) overweight/obese women who received letrozole 2.5 mg/day, and the metformin arm (n = 15) overweight/obese women who received letrozole 2.5 mg/day plus metformin (2000 ± 500 mg/day). The intervention duration was 6 months. Blood samples were obtained at baseline and 6 months after intervention for the measurement of serum estradiol, leptin, osteocalcin levels, fasting blood glucose concentration, and serum insulin. RESULTS: After the intervention and as compared to the control arm, the metformin arm showed a significantly lower ratio to the baseline (significant reduction) for estradiol (p = 0.0433), leptin (p < 0.0001), fasting blood glucose (p = 0.0128), insulin (p = 0.0360), osteocalcin serum levels (p < 0.0001), and the homeostatic model assessment of insulin resistance "HOMA-IR" value (p = 0.0145). There was a non-significant variation in the lactate ratio to the baseline among the three study arms (p = 0.5298). CONCLUSION: Metformin may exert anti-cancer activity by decreasing the circulating estradiol, leptin, and insulin. Metformin might represent a safe and promising adjuvant therapy to letrozole in overweight/obese postmenopausal women with breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05053841/Registered September 23, 2021 - Retrospectively.


Assuntos
Neoplasias da Mama , Metformina , Feminino , Humanos , Letrozol/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Metformina/uso terapêutico , Leptina , Estradiol/uso terapêutico , Projetos Piloto , Sobrepeso/complicações , Sobrepeso/tratamento farmacológico , Glicemia , Pós-Menopausa , Estudos Retrospectivos , Osteocalcina/uso terapêutico , Obesidade/tratamento farmacológico , Insulina , Biomarcadores
3.
Support Care Cancer ; 30(9): 7281-7292, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35596774

RESUMO

BACKGROUND AND OBJECTIVE: Paclitaxel and doxorubicin are associated with neurotoxicity and cardiotoxicity respectively. This study aimed at investigating the role of alpha-lipoic acid (ALA) in counteracting paclitaxel-induced neuropathy and doxorubicin-associated cardiotoxicity in women with breast cancer. PATIENTS AND METHODS: This randomized double-blind placebo-controlled prospective study included 64 patients with breast cancer who were randomized into control group (n = 32) which received 4 cycles of doxorubicin plus cyclophosphamide (every 21 days) followed by weekly doses of paclitaxel for 12 weeks plus placebo tablets once daily and ALA group (n = 32) which received the same chemotherapeutic regimen plus ALA 600 once daily for 6 months. Patients were assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4.0) for grading of neuropathy and by 12-item neurotoxicity questionnaire (Ntx-12). The assessment included also echocardiography and evaluation of serum levels of brain natriuretic peptide (BNP), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), and neurotensin (NT). Data were analyzed by paired and unpaired t-test, Mann-Whitney U test, and chi-square test. RESULTS: As compared to placebo, ALA provoked significant improvement in NCI-CTCAE neuropathy grading and Ntx-12 score after the end of 9th and 12th weeks of paclitaxel intake (p = 0.039, p = 0.039, p = 0.03, p = 0.004, respectively). At the end of the chemotherapy cycles, ALA resulted in significant decline in serum levels of BNP, TNF-α, MDA, and neurotensin (p < 0.05) as compared to baseline data and placebo. CONCLUSION: Alpha-lipoic acid may represent a promising adjuvant therapy to attenuate paclitaxel-associated neuropathy and doxorubicin-induced cardiotoxicity in women with breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03908528.


Assuntos
Neoplasias da Mama , Síndromes Neurotóxicas , Doenças do Sistema Nervoso Periférico , Ácido Tióctico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Doxorrubicina , Feminino , Humanos , Neurotensina/sangue , Síndromes Neurotóxicas/etiologia , Paclitaxel , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Estudos Prospectivos , Ácido Tióctico/uso terapêutico , Fator de Necrose Tumoral alfa/sangue
4.
Eur J Clin Pharmacol ; 77(12): 1825-1834, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34218304

RESUMO

PURPOSE: Investigating the efficacy and safety of rupatadine (RUP) versus montelukast (MON) as adjuvant therapy for patients with rheumatoid arthritis (RA). METHODS: From December 2018 to December 2019, 75 patients with active RA were enrolled in this randomized double-blind placebo-controlled study. The patients were randomized into three groups (n = 25 in each group); methotrexate (MTX) group which received MTX 15-25 mg/week plus placebo tablet once daily; MTX/RUP group which received MTX plus RUP 10 mg once daily; and MTX/MON group which received MTX plus MON 10 mg once daily. The treatment duration was 3 months. At baseline and 3 months after treatment, blood samples were collected for the biochemical analysis of high-sensitivity C-reactive protein (hs-CRP), interleukins 8 and 17 (IL-8, IL-17), E-selectin, and clusterin (CLU) levels. Clinical and functional assessments using Disease Activity Score-CRP (DAS28-CRP) and Multidimensional Health Assessment Questionnaire (MDHAQ) were performed. RESULTS: Both RUP and MON produced clinical and functional improvements which were translated by significant improvements in DAS28-CRP score and MDHAQ. Rupatadine significantly reduced all measured parameters (P < 0.05) except for IL-17 and CLU. Montelukast significantly decreased all measured variables (P < 0.05) except for E-selectin. Interleukin-8 was positively correlated with IL-17 and CLU, while hs-CRP was positively correlated with E-selectin and body mass index (BMI). Both drugs were well tolerated; somnolence was the common side effect for RUP. No neuropsychiatric events were reported with MON. CONCLUSION: Rupatadine or montelukast may serve as a potential adjuvant therapy for patients with rheumatoid arthritis secondary to the preliminary evidence of efficacy and safety. ClinicalTrials.gov identifier NCT03770923, December 10, 2018.


Assuntos
Acetatos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Ciclopropanos/uso terapêutico , Ciproeptadina/análogos & derivados , Antagonistas dos Receptores Histamínicos/uso terapêutico , Imunossupressores/uso terapêutico , Antagonistas de Leucotrienos/uso terapêutico , Quinolinas/uso terapêutico , Sulfetos/uso terapêutico , Acetatos/administração & dosagem , Acetatos/efeitos adversos , Adulto , Índice de Massa Corporal , Proteína C-Reativa/efeitos dos fármacos , Clusterina/efeitos dos fármacos , Ciclopropanos/administração & dosagem , Ciclopropanos/efeitos adversos , Ciproeptadina/administração & dosagem , Ciproeptadina/efeitos adversos , Ciproeptadina/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Selectina E/efeitos dos fármacos , Egito , Feminino , Antagonistas dos Receptores Histamínicos/administração & dosagem , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Interleucinas/metabolismo , Antagonistas de Leucotrienos/administração & dosagem , Antagonistas de Leucotrienos/efeitos adversos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Sulfetos/administração & dosagem , Sulfetos/efeitos adversos
5.
Int J Vitam Nutr Res ; 91(1-2): 56-62, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31433269

RESUMO

Background: Elevated homocysteine levels and malnutrition are frequently detected in hemodialysis patients and are believed to exacerbate cardiovascular comorbidities. Omega-3 fatty acids have been postulated to lower homocysteine levels by up-regulating metabolic enzymes and improving substrate availability for homocysteine degradation. Additionally, it has been suggested that prevention of folate depletion by vitamin E consumption decreases homocysteine levels. However, data on the effect of omega-3 fatty acids and/or vitamin E on homocysteine levels and nutritional status have been inconclusive. Therefore, this study was planned to examine the effect of combined supplementation of fish oil, as a source of omega-3 fatty acids, with wheat germ oil, as a source of vitamin E, on homocysteine and nutritional indices in hemodialysis patients. Methods: This study was a randomized, double-blind, placebo-controlled trial. Forty-six hemodialysis patients were randomly assigned to two equally-sized groups; a supplemented group who received 3000 mg/day of fish oil [1053 mg omega-3 fatty acids] plus 300 mg/day of wheat germ oil [0.765 mg vitamin E], and a matched placebo group who received placebo capsules for 4 months. Serum homocysteine and different nutritional indices were measured before and after the intervention. Results: Twenty patients in each group completed the study. At the end of the study, there were no significant changes in homocysteine levels and in the nutritional indices neither in the supplemented nor in the placebo-control groups (p > 0.05). Conclusions: Fish oil and wheat germ oil combination did not produce significant effects on serum homocysteine levels and nutritional indices of hemodialysis patients.


Assuntos
Ácidos Graxos Ômega-3 , Óleos de Peixe , Suplementos Nutricionais , Método Duplo-Cego , Homocisteína , Humanos , Avaliação Nutricional , Óleos de Plantas , Diálise Renal
6.
Curr Ther Res Clin Exp ; 94: 100625, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34306265

RESUMO

BACKGROUND: There are differences of opinion about both the most effective combined therapeutic strategy and the clinical benefit of inhaled corticosteroids in nonasthmatic patients with chronic obstructive pulmonary disease. Furthermore, many inflammatory cytokines are reportedly correlated with severity of the disease. OBJECTIVES: To compare the effectiveness of long acting ß-agonist + long-acting muscarinic antagonist (LABA + LAMA) versus LABA + inhaled corticosteroid and LAMA + inhaled corticosteroid in nonasthmatic patients with moderate-to-severe chronic obstructive pulmonary disease. To assess the changes that occurred in plasma concentrations of tumor necrosis factor α, fibrinogen, and interleukin 6, and correlate these with disease activity. METHODS: In this pilot study, 45 nonasthmatic patients with moderate to severe chronic obstructive pulmonary disease were randomized into 3 groups with 15 patients in each group. Group I (LABA + inhaled corticosteroid) received formoterol/budesonide, group II (LAMA + inhaled corticosteroid) received tiotropium/budesonide and group III (LABA + LAMA) received formoterol/tiotropium for 12 weeks. Patients were assessed initially and then at 4 and 12 weeks by measuring the changes that occurred in forced expiratory volume in 1 second as a percent of predicted and in the modified Medical Research Council dyspnea scale. Plasma concentrations of tumor necrosis factor α, fibrinogen, and interleukin 6 were simultaneously measured. RESULTS: The 3 study groups were statistically similar with respect to their demographic data and disease characteristics. All therapeutic options produced an improvement in forced expiratory volume in 1 second as a percent of predicted and in the modified Medical Research Council dyspnea scale as well as a reduction in plasma concentrations of the inflammatory markers. The effects produced by the three therapeutic combinations on forced expiratory volume in 1 second as a percent of predicted, plasma tumor necrosis factor α, interleukin 6, and fibrinogen concentrations were statistically similar after 4 and 12 weeks (4 weeks after treatment: P = 0.358, P = 0.284, P = 0.155, and P = 0.155, respectively, and 12 weeks after treatment: P = 0.710, P = 0.773, P = 0.240, and P = 0.076, respectively). CONCLUSIONS: In nonasthmatic patients with moderate to severe chronic obstructive pulmonary disease, the 3 therapeutic combinations showed similar effectiveness. The results of this pilot study also suggest that inflammatory markers can be used to track disease activity. Clinicaltrials.gov identifier: NCT04520230. (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX).

7.
Curr Ther Res Clin Exp ; 95: 100654, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34925649

RESUMO

Objective: This study aimed at evaluating the effects of candesartan and ramipril on liver fibrosis in patients with chronic hepatitis C. Methods: This randomized controlled prospective study involved 64 patients with chronic hepatitis C and liver fibrosis. Participants were randomized into 3 groups: group I (control group; n = 21), members of which received traditional therapy only; group 2 (ramipril group; n = 21), members of which received traditional therapy plus 1.25 mg/d oral ramipril; and group 3 (candesartan group; n = 22), members of which received traditional therapy plus 8 mg/d oral candesartan. Patients were assessed at baseline and 6 months after intervention through measuring of liver stiffness (Fibro-Scan; Echosens, Paris, France); evaluation of the serum levels of hyaluronic acid and transforming growth factor beta-1; and calculation of indices of liver fibrosis, including fibrosis index based on the 4 factors and aspartate transaminase-to-platelet-ratio index. Data were analyzed using paired t test and 1-way ANOVA followed by Tukey's honest significant difference test for multiple pairwise comparisons. Results: At baseline, the 3 study groups were statistically similar in demographic and laboratory data. After treatment, the 3 study groups showed significant decrease in liver stiffness, serum levels of hyaluronic acid and transforming growth factor beta-1, and indices of liver fibrosis compared with baseline data (P < 0.001). Six months after treatment, patients taking ramipril and candesartan showed significant improvement in all measured parameters compared with the control group. Additionally, the candesartan-treated group showed significant decrease in liver stiffness, biomarkers, and indices of liver fibrosis compared with ramipril recipients. Conclusions: The administration of ramipril and candesartan in patients with chronic hepatitis C with hepatic fibrosis was well tolerated and effective in improving liver fibrosis. angiotensin II receptor 1 (AT1) antagonist candesartan maintained antifibrotic effects more effectively than ramipril and may represent a safe and effective therapeutic strategy for liver fibrosis in patients with chronic liver diseases. ClinicalTrials.gov identifier: NCT03770936. (Curr Ther Res Clin Exp. 2022; 83:XXX-XXX) © 2022 Elsevier HS Journals, Inc.

8.
J Appl Biomed ; 19(1): 62-72, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-34907717

RESUMO

This study aimed at evaluating the role played by insulin resistance, lipid metabolism disorder, oxidative stress, resistin, vaspin, Interleukin-18 and asymmetric dimethyl arginine as a marker for endothelial dysfunction in the pathogenesis of preeclampsia. This prospective observational cohort study involved 60 women who were classified into: 20 non-pregnant women (group 1 or control group), 20 normally pregnant women (group 2) and 20 preeclamptic women (group 3) at their third trimester. The pregnant women were assessed at their third trimester and further re-evaluated four weeks after delivery. The assessment included demography, assessment of proteinuria and urinary protein to creatinine ratio, blood pressure measurement and assessment of fasting blood glucose, fasting insulin level, lipid panel and the circulating levels of malondialdehyde, resistin, vaspin, interleukin-18 and asymmetric dimethyl arginine. Preeclamptic women showed more atherogenic lipid profile, significantly higher Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and significantly elevated levels of malondialdehyde, resistin, vaspin and interleukin-18 than the other study groups. Serum asymmetric dimethyl arginine concentration showed non-significant difference among the three study groups. The levels of resistin and vaspin showed significant decrease four weeks postpartum in preeclamptic group. We concluded that, preeclampsia was associated with insulin resistance, dyslipidemia, oxidative stress, inflammation and significant changes in adipokines; resistin and vaspin. Furthermore, the significant increase in the serum levels of resistin and vaspin at the third trimester and their significant decline four weeks postpartum in preeclamptic group focus the attention on the role played by these adipokines in the pathogenesis of preeclampsia.


Assuntos
Adipocinas , Resistência à Insulina , Pré-Eclâmpsia , Adipocinas/metabolismo , Arginina , Biomarcadores , Citocinas/metabolismo , Feminino , Humanos , Resistência à Insulina/fisiologia , Interleucina-18 , Lipídeos , Masculino , Malondialdeído , Período Pós-Parto , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/metabolismo , Gravidez , Diagnóstico Pré-Natal , Estudos Prospectivos , Resistina
9.
Indian J Med Res ; 152(4): 393-400, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33380704

RESUMO

BACKGROUND & OBJECTIVES: : Rheumatoid artherits (RA) is a refractory disease and the imbalance between pro- and anti-inflammatory cytokines in favor of pro-inflammatory cytokines has been implicated in pathogenesis of RA. In this context, the aim of the present study was to compare the anti-inflammatory and antioxidant effects of candesartan, an angiotensin-receptor blocker, and atorvastatin in RA patients. METHODS: : In this single-blinded parallel randomized placebo controlled study, the patients recruited between December 2017 and May 2018 were categorized into three groups: group 1 included 15 RA patients who served as control group and received traditional therapy (+ placebo); group 2 included 15 RA patients who received traditional therapy + candesartan (8 mg/day); and group 3 included 15 patients who received traditional therapy + atorvastatin (20 mg/day) for three months. Clinical status in RA patients was evaluated by Disease Activity Score 28 (DAS28), Health Assessment Questionnaire-Disability Index (HAQ-DI) and morning stiffness before and three months after treatment. All groups were subjected to biochemical analysis of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), tumour necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß) and malondialdehyde (MDA) before and three months after treatment. RESULTS: : Both candesartan and atorvastatin treated groups showed significant decrease in serum levels IL-1ß and TNF-α, acute-phase reactants (CRP and ESR), number of swollen joint and patient global assessment. This was also associated with improvement in disease activity and quality of life regarding DAS28 and HAQ-DI as compared to baseline data and the control group. Atorvastatin group showed significant decrease in the serum level of oxidative stress marker (MDA). INTERPRETATION & CONCLUSIONS: : Both candesartan and atorvastatin showed anti-inflammatory effect and immunomodulatory effects leading to improvement in clinical status and disease activity in RA patients. However, atorvastatin was superior to candesartan through its anti-oxidant effect.


Assuntos
Artrite Reumatoide , Inibidores de Hidroximetilglutaril-CoA Redutases , Antagonistas de Receptores de Angiotensina/uso terapêutico , Angiotensinas/uso terapêutico , Anti-Inflamatórios , Artrite Reumatoide/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Qualidade de Vida , Fator de Necrose Tumoral alfa
10.
Psychother Psychosom ; 87(6): 331-339, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30205379

RESUMO

BACKGROUND: There is evidence for an association between major depressive disorder (MDD) and both inflammatory and phosphodiesterase (PDE) pathways. This study aimed to evaluate the adjunct role of the PDE inhibitor pentoxifylline (PTX), a compound with anti-inflammatory properties, in the treatment of adult patients with MDD. METHODS: This was a prospective, 12-week, double-blind study of parallel groups. Eighty adult outpatients who met the DSM-IV criteria for MDD participated in the trial. Patients were required to have a baseline Hamilton Rating Scale for Depression (HAM-D) score of at least 18. Patients were allocated randomly: 40 received escitalopram 20 mg/day plus placebo while the other 40 received escitalopram 20 mg/day plus PTX (400 mg b.i.d.). Patients were assessed by a psychiatrist at baseline, and 4, 8, and 12 weeks after the medication had been started. The serum levels of TNF-α, IL-6, IL-10, BDNF, 8-OHdG, and serotonin were measured at baseline and after therapy. RESULTS: After 8 and 12 weeks, the PTX group showed a statistically significantly greater improvement in HAM-D score compared to the control group (least squares mean difference [LSMD] -3.29, p = 0.000 and LSMD -3.49, p = 0.000, respectively). Moreover, the PTX group showed a statistically significantly greater reduction in the serum levels of TNF-α, IL-6, IL-10, and 8-OHdG along with a statistically significant increase in the levels of BDNF and serotonin in comparison with the control group after the treatment. CONCLUSION: The findings of this study suggest that PTX could be a promising adjunct to antidepressants in the treatment of MDD patients.


Assuntos
Citalopram/administração & dosagem , Citocinas/sangue , Transtorno Depressivo Maior/tratamento farmacológico , Pentoxifilina/administração & dosagem , Inibidores de Fosfodiesterase/administração & dosagem , Adulto , Citalopram/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Egito , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pentoxifilina/efeitos adversos , Inibidores de Fosfodiesterase/efeitos adversos , Estudo de Prova de Conceito , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Adulto Jovem
11.
Int J Colorectal Dis ; 33(12): 1675-1683, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29931409

RESUMO

PURPOSE: Peripheral sensory neuropathy is the most prominently reported adverse effect of oxaliplatin. The purpose of this study was to evaluate metformin role in oxaliplatin-induced neuropathy. PATIENTS AND METHODS: From November 2014 to May 2016, 40 patients with stage III colorectal cancer completed 12 cycles of FOLFOX-4 regimen. Twenty patients in the control arm received FOLFOX-4 regimen only, and 20 patients in the metformin arm, received the same regimen along with metformin 500 mg three times daily. The metformin efficacy was evaluated using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4.0), a12-item neurotoxicity questionnaire (Ntx-12) from the validated Functional Assessment of Cancer Therapy/Gynecologic Oncology Group and, the brief pain inventory short form "worst pain" item. In addition to neurotensin, malondialdehyde and interleukin-6 serum levels assessment. RESULTS: At the end of the 12th cycle, there were less patients with grade 2 and 3 neuropathy in metformin arm as compared to control arm. (60 versus 95%, P = 0.009) In addition, metformin arm showed significantly higher total scores of Ntx-12 questionnaire than control arm (24.0 versus 19.2, P < 0.001). Furthermore, the mean pain score in metformin arm was significantly lower than those of control arm, (6.7 versus 7.3, P = 0.005). Mean serum levels of malondialdehyde and neurotensin were significantly lower in metformin arm after the 6th and the 12th cycles. CONCLUSION: Metformin may be a promising drug in protecting colorectal cancer patients against oxaliplatin-induced chronic peripheral sensory neuropathy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Metformina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Oxaliplatina/efeitos adversos , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Neoplasias Colorretais/patologia , Egito , Fluoruracila/efeitos adversos , Humanos , Leucovorina/efeitos adversos , Metformina/efeitos adversos , Estadiamento de Neoplasias , Fármacos Neuroprotetores/efeitos adversos , Compostos Organoplatínicos/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/fisiopatologia , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
12.
J Adolesc ; 37(4): 473-82, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24793395

RESUMO

This article explores the effect of tracked education in upper secondary on voting behaviour. It discusses two causal mechanisms that link tracked education to greater disparities of political participation: the curriculum and peer socialization. Data of Waves 1, 2, 5 and 7 of the Longitudinal Study of Young People in England (LSYPE) is used to assess the hypothesis that educational track has an independent effect on voting. Controlling for several pre- and post-track influences, the paper shows that students who have taken vocational courses in less prestigious schools indeed have lower reported voting levels at age 20 than those who have pursued an academic qualification (A levels) in prestigious schools. It is proposed that the effect of tracked education on political participation is likely to vary across Europe and that this variation may well be explained by differences across Europe in the extent to which the academic and vocational tracks are integrated, both in terms of the curriculum and in their social intake.


Assuntos
Política , Adolescente , Escolaridade , Inglaterra/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Participação Social/psicologia , Adulto Jovem
13.
Indian J Anaesth ; 68(7): 616-622, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39081911

RESUMO

Background and Aims: Postoperative pain after hip surgeries in children could be classified as severe, requiring combined intra- and postoperative opioid analgesia with regional blocks. This study was carried out to investigate ultrasound-guided pericapsular nerve group (PENG) block versus ultrasound-guided erector spinae plane (ESP) block for pain management after paediatric hip surgery. The primary objective was to assess the time of the first request for morphine rescue analgesia. Methods: In this randomised study, 56 children scheduled for elective unilateral hip surgery were distributed randomly to ESP and PENG groups. Intraoperative haemodynamics, fentanyl consumption, postoperative pain measurement, morphine consumption, time of first rescue analgesia, adverse effects and parents' satisfaction score were studied. The primary outcome was the time of the first request for morphine rescue analgesia. The Chi-square test, Student's t-test and the Mann-Whitney U test were used, where applicable, to compare the groups. Results: The time to first rescue analgesia was significantly longer in Group ESP than in Group PENG (P < 0.001), with significantly higher postoperative morphine consumption in Group PENG than in Group ESP (P = 0.04). The pain scores of Group ESP were lower than those of Group PENG at 2 and 4 h postoperatively (P = 0.006 and P < 0.001, respectively). At 8 h postoperatively, the score was significantly higher in Group ESP than in Group PENG (P = 0.005). Other outcomes were comparable between both groups (P > 0.05). Conclusion: ESP and PENG could be both effective for intraoperative and postoperative analgesia in paediatric hip surgeries, but the ESP block prolonged the time of first rescue analgesia more than the PENG block.

14.
Am J Med ; 137(1): 55-64, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37832758

RESUMO

BACKGROUND: Complications associated with liver cirrhosis are various and potentially fatal. The treatment options to counteract hepatic decompensation are limited. Therefore, the study aimed to explore the use of allopurinol in preventing the recurrence of liver cirrhosis-related complications. METHODS: One hundred patients with hepatic decompensation were randomized into 1:1 ratio to receive either allopurinol 300 mg or placebo tablets once daily for 6 months. The primary endpoint was the incidence of cirrhosis-related complications (overt ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatorenal syndrome, and hepatic encephalopathy). RESULTS: Six months following treatment, allopurinol reduced the relative risk (RR) of any first complication experienced after enrollment by 56% (hazard ratio [HR] 0.44; 95% confidence interval [CI], 0.27-0.62); P ˂ .001). Allopurinol decreased the RR of overt ascites by 67% (HR 0.33; 95% CI, 0.0098-0.94); P = .039] and reduced the RR of spontaneous bacterial peritonitis by about 75% (HR 0.25; 95% CI, 0.05-0.76; P = .01). Likewise, allopurinol was linked to an 80% reduction in the RR of developing hepatorenal syndrome (HR 0.2; 95% CI, 0.04-0.87; P = .033). CONCLUSION: Allopurinol significantly decreased the recurrence of overall liver cirrhosis-related complications. Therefore, allopurinol may constitute a promising agent for patients with hepatic decompensation. These positive outcomes could be a result of its ability to reduce bacterial translocation and inflammation. GOV IDENTIFIER: NCT005545670.


Assuntos
Varizes Esofágicas e Gástricas , Síndrome Hepatorrenal , Peritonite , Humanos , Alopurinol/uso terapêutico , Varizes Esofágicas e Gástricas/complicações , Ascite/etiologia , Ascite/prevenção & controle , Síndrome Hepatorrenal/tratamento farmacológico , Síndrome Hepatorrenal/etiologia , Síndrome Hepatorrenal/prevenção & controle , Hemorragia Gastrointestinal/etiologia , Cirrose Hepática/complicações , Peritonite/prevenção & controle , Peritonite/complicações
15.
J Voice ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39043533

RESUMO

PURPOSE: This study aimed to assess the outcomes of posterior cordotomy in cases with bilateral abductor vocal fold immobility (BAVFI), either by radiofrequency or CO2 laser. METHODS: This prospective comparative randomized study included 80 patients with BAVFI of different etiologies. They were divided randomly into two groups. Group A included 44 patients for whom radiofrequency was used for posterior cordotomy, while the other group (group B) included 36 patients managed by CO2 laser-assisted posterior cordotomy. RESULTS: The postoperative respiratory chink improved significantly in both groups, with a significant improvement in the dyspnea, especially in group B. The postoperative voice handicapped VHI-10 scores showed significant deterioration in both groups. CONCLUSIONS: CO2 laser and radiofrequency-assisted posterior cordotomy were effective and safe for managing cases with BAVFI. Moreover, the CO2 laser has the upper hand regarding breathing and exercise tolerance outcomes, significantly impacting the quality of life.

16.
J Opioid Manag ; 19(4): 313-320, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37644789

RESUMO

OBJECTIVES: This study aimed to evaluate the analgesic effect of the ultrasound-guided pericapsular nerve group (PENG) block in hip arthroplasty (HA) surgery. DESIGN: A prospective double-blinded, randomized study. SETTING: Tertiary institutional clinical care. PARTICIPANTS: Fifty patients, more than 50 years old of both genders, were chosen according to the American Society of Anesthesiologists classification, with physical status I-III, and scheduled for unilateral HA surgeries. INTERVENTIONS: Patients were randomized to receive either a sham PENG block with 20 mL of normal saline (control group) or a PENG block with 20 mL of bupivacaine 0.25 percent (PENG group). MAIN OUTCOME MEASURES: From the onset of the first request for rescue opioid analgesia, preoperative pain scores before and after block (at rest and with a raised straight leg), the incidence of quadriceps weakness after the block, intraoperative fentanyl consumption, post-operative pain scores, and morphine consumption, besides the presence and frequency of adverse events, were recorded. RESULTS: The patients undergoing PENG block with bupivacaine had prolonged durations before the first analgesic request, lower perioperative pain scores, less intraoperative rescue fentanyl, and less post-operative morphine consumption than the control group, with nonsignificant motor weakness after the block and similar adverse events. CONCLUSIONS: The PENG block provided effective perioperative analgesia for HA with prolonged duration of analgesia, nonsignificant motor effects, reduced perioperative opioids consumption, and no major side effects.


Assuntos
Anestésicos Locais , Artroplastia de Quadril , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Anestésicos Locais/efeitos adversos , Analgésicos Opioides/efeitos adversos , Artroplastia de Quadril/efeitos adversos , Estudos Prospectivos , Nervo Femoral , Bupivacaína/efeitos adversos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Morfina/uso terapêutico , Fentanila/uso terapêutico
17.
Indian J Anaesth ; 67(10): 885-892, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38044925

RESUMO

Background and Aims: Optimal analgesia after total knee arthroplasty (TKA) enhances patients' and surgical outcomes. The study investigated the ultrasound-guided genicular nerve block versus the periarticular infiltration in TKA. Methods: Eighty-eight patients aged above 50 years scheduled for unilateral TKA were randomised as: Group 1 received intraoperative periarticular infiltration (0.5 mL adrenaline [4.5 µg/mL], 20 mL bupivacaine 0.5% with 89.5 mL saline) and Group 2 received immediate postoperative genicular nerve block (15 mL bupivacaine 0.25% with 2.5 g/mL adrenaline). The postoperative morphine consumption was during the first two postoperative days the primary outcome. The secondary outcomes were time to rescue analgesia, pain scores and functional outcomes. The comparison between groups was performed using the Chi-square test, the Student's t-test and the Mann-Whitney U test, as appropriate. Results: The postoperative morphine consumption during the first two postoperative days and pain scores at rest at 12 h postoperatively were less in Group 1 than in Group 2 (P < 0.001). Pain scores during movement on the first postoperative day were lower in the periarticular group than the genicular group at 6, 12 and 24 h (P < 0.001). At 18 h, pain scores were higher in the periarticular group than in the genicular group at rest and movement (P < 0.001). Quadriceps motor strength scores were comparable between groups (P > 0.05). The knee range of motion and time up and go test during both days showed a statistically significant difference in the periarticular group compared to the genicular group (P < 0.05). Conclusion: Periarticular infiltration and genicular nerve block yield effective postoperative analgesia and functional outcomes after TKA without motor affection.

18.
Saudi Med J ; 43(1): 37-44, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35022282

RESUMO

OBJECTIVES: To investigate the anti-tumor activity and tolerability of celecoxib as an adjuvant therapy for patients with metastatic colorectal cancer (CRC). METHODS: In this randomized controlled study, 54 patients with metastatic CRC were randomized into 2 groups; the control group (n=28) which received 6 cycles of folinic acid, fluorouracil and irinotecan (FOLFIRI) regimen (5-flourouracil, leucovorin, irinotecan), and the celecoxib group (n=26) which received 6 cycles of FOLFIRI regimen plus celecoxib 200 mg twice daily. The study duration was 3 months. Patients were assessed at baseline and at the end of intervention through the Response Evaluation Criteria in Solid Tumors objective response rate (ORR) and through evaluating the serum concentrations of vascular endothelial growth factor (VEGF), soluble factor-related apoptosis (sFAS), sFAS ligand (sFASL), and epithelial neutrophil-activating peptide -78 (ENA-78/CXCL5). Common Terminology Criteria for Adverse Events version 6.0 was used for evaluating drug-related toxicity. RESULTS: After intervention, celecoxib/FOLFIRI arm showed significant elevation in ORR as compared to FOLFIRI arm (p=0.001). As compared to FOLFIRI arm, celecoxib/FOLFIRI arm showed significantly lower VEGF (p<0.001), CXCL5 (p<0.001), and sFASL (p<0.001) serum levels and significantly higher sFAS serum level and sFAS/FASL ratio (p<0.001). Furthermore, celecoxib/FOLFIRI arm showed significantly higher progression-free survival and one-year overall survival when compared to FOLFIRI arm. CONCLUSION: Celecoxib plus chemotherapy may represent an effective and safe synergetic protocol for patients with metastatic CRC.Clinicaltrial.gov ID:NCT03645187.


Assuntos
Neoplasias Colorretais , Fator A de Crescimento do Endotélio Vascular , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/uso terapêutico , Celecoxib/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila , Humanos , Leucovorina
19.
J Cardiovasc Pharmacol Ther ; 27: 10742484221132671, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36282078

RESUMO

BACKGROUND: Pulmonary hypertension (PHT) is common in ß-thalassemia patients due to hemolysis, iron overload and diminished nitric oxide (NO) levels. Biochemical markers can help to understand the pathophysiology and to introduce new therapies for this condition. AIM: This study aimed to evaluate the effectiveness of L-arginine and sildenafil in thalassemia children with PHT at both clinical and biochemical levels. METHODS AND RESULTS: In a randomized controlled study, 60 ß-thalassemia major children with PHT were divided into 3 equal groups; Control group (Conventional thalassemia and PHT management), L-arginine group (Conventional + Oral L-arginine 0.1 mg.kg-1 daily), and sildenafil group (Conventional + Oral sildenafil 0.25 mg.kg-1 two times a day) for 60 days. Tricuspid Regurgitant Jet Velocity (TRJV) with Doppler echocardiography along with serum levels of NO, asymmetric dimethylarginine (ADMA), interleukin 1-beta (IL-1ß), E-selectin, and visfatin were followed-up at baseline, 30, and 60 days after treatment. Both drugs reduced the TRJV significantly. NO was significantly higher in both L-arginine and sildenafil groups after 60 days compared to baseline, while visfatin levels were lower. Only L-arginine reduced ADMA levels compared to baseline, while sildenafil did not. E-selectin and IL-1ß levels did not change remarkably by both drugs. NO and TRJV showed significant negative correlations in both treatment groups. CONCLUSION: L-arginine and sildenafil could clinically ameliorate chronic PHT whereas, L-arginine showed superiority to sildenafil on some biochemical markers.


Assuntos
Hipertensão Pulmonar , Talassemia , Insuficiência da Valva Tricúspide , Talassemia beta , Criança , Humanos , Talassemia beta/diagnóstico , Talassemia beta/tratamento farmacológico , Citrato de Sildenafila/efeitos adversos , Selectina E , Nicotinamida Fosforribosiltransferase , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/tratamento farmacológico , Óxido Nítrico , Arginina , Biomarcadores , Interleucina-1
20.
Anat Cell Biol ; 55(3): 341-355, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36008129

RESUMO

As a synthetic analog of codeine, tramadol is often prescribed to treat mild to moderate pains. This study was designed to estimate and compare the histological effect of tramadol on testes of both juvenile and adult male albino mice. A total number of 40 healthy male albino mice were classified into two main groups as follows: group I (juvenile group, includes 20 mice aged three weeks) subdivided equally into group Ia (control group received isotonic saline) and group Ib (tramadol-treated group received 40 mg/kg/d tramadol orally for 30 days); group II (adult group, includes 20 mice aged two months) subdivided equally into group IIa (control group received isotonic saline) and group IIb (tramadol-treated group). Juvenile and adult tramadol-treated groups showed numerous testicular changes, including blood vessels congestion, widening of intercellular spaces, vacuolization in interstitial tissues, luminal germ cells exfoliation, and increased expression of caspase-3 that indicated cellular apoptosis. In the ultrastructural examination, spermatogenic cells degenerated with the frequent appearance of apoptotic cells. Sertoli cells showed vacuolations, large lipid droplets, and disrupted intercellular cell junctions. These observed testicular changes were markedly observed in the juvenile group. Testicular abnormalities and apoptotic changes can be caused by tramadol administration. These abnormalities are more common in juvenile mice.

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