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1.
Biomed Khim ; 66(1): 71-76, 2020 Jan.
Artigo em Russo | MEDLINE | ID: mdl-32116228

RESUMO

The pharmacokinetics and bioavailability of a derivative of 3,7-diazabicyclo[3.3.1]nonane exhibiting a nootropic effect, were studied after a single dose to rats. The pharmacokinetics of the compound was studied after oral and intravenous administration to 270 male rats Sprague Dawley at doses of 2.5 mg/kg, 13 mg/kg and 25 mg/kg. Its distribution in organs and tissues (brain, thymus, heart, lungs, liver, kidneys, and spleen) was also investigated. It was found that after a single intravenous administration, the investigated substance was determined in the blood of animals for 24 h; the half-life was 4.69 h. The relative bioavailability of the 3,7-diazabicyclo[3.3.1]nonane derivative after oral administration was 42.3%, thus suggesting the prospect of creating dosage forms for oral administration. After a single oral administration, the dose dependence of AUC0-t was exponential. The substance is characterized by heterogeneous distribution in the body with preferential accumulation mainly in well-vascularized tissues.


Assuntos
Compostos Aza/farmacocinética , Nootrópicos/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Meia-Vida , Injeções Intravenosas , Masculino , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
2.
Br J Anaesth ; 124(3): 314-323, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32000978

RESUMO

BACKGROUND: In surgical patients undergoing general anaesthesia, coughing at the time of extubation is common and can result in potentially dangerous complications. We performed a systematic review and meta-analysis to assess the efficacy and safety of i.v. lidocaine administration during the perioperative period to prevent cough and other airway complications. METHODS: We searched Medical Literature Analysis and Retrieval System, Excerpta Medica database, and Cochrane Central Register of Controlled Trials for RCTs comparing the perioperative use of i.v. lidocaine with a control group in adult patients undergoing surgery under general anaesthesia. The RCTs were assessed using risk-of-bias assessment, and the quality of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). RESULTS: In 16 trials (n=1516), the administration of i.v. lidocaine compared with placebo or no treatment led to large reductions in post-extubation cough (risk ratio [RR]: 0.64; 95% confidence interval [CI]: 0.48-0.86) and in postoperative sore throat at 1 h (RR: 0.46; 95% CI: 0.32-0.67). There was no difference in incidence of laryngospasm (risk difference [RD]: 0.02; 95% CI: -0.07 to 0.03) or incidence of adverse events related to the use of lidocaine. CONCLUSIONS: The use of i.v. lidocaine perioperatively decreased airway complications, including coughing and sore throat. There was no associated increased risk of harm.


Assuntos
Anestesia Geral/efeitos adversos , Anestésicos Locais/administração & dosagem , Tosse/prevenção & controle , Lidocaína/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Anestésicos Locais/uso terapêutico , Tosse/etiologia , Remoção de Dispositivo/efeitos adversos , Humanos , Injeções Intravenosas , Intubação Intratraqueal/efeitos adversos , Lidocaína/uso terapêutico , Assistência Perioperatória/métodos , Faringite/etiologia , Faringite/prevenção & controle
3.
Crit Care Resusc ; 22(1): 80-82, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32102646

RESUMO

BACKGROUND: Due to the lack of double-blind randomised controlled trials, the true effect of intravenous sodium bicarbonate therapy in ICU patients with metabolic acidosis remains unclear. METHODS: We diluted 100 mL 8.4% sodium bicarbonate in 150 mL 5% dextrose (D5W) within a 250 mL polyolefin bag after removing 100 mL. We asked ICU clinicians to inspect a 250 mL bag containing sodium bicarbonate or a 250 mL bag where 100 mL of D5W had been removed and then returned. The bags were attached to intravenous giving sets. We asked participants to identify the contents of the bags. RESULTS: Among 60 participants (39 nursing staff [65%], 20 medical staff [33.3%] and one pharmacist), 36 (60%) answered correctly. The Cohen κ for agreement between test bag content and participants' answers was 0.20 (95% CI, -0.05 to 0.45; P = 0.12), implying the answers were correct by chance. In the group of 28 participants who indicated they used a clue to help them decide their answer, 15 (53.6%) answered correctly, whereas in the remainder (n = 32), 21 (65.6%) answered correctly (P = 0.49). CONCLUSION: When 100 mL of 8.4% sodium bicarbonate were diluted in 150 mL of D5W within a 250 mL polyolefin bag, clinicians were unable to correctly identify the contents of the bags. Our findings imply that sodium bicarbonate therapy can be successfully blinded.


Assuntos
Acidose/tratamento farmacológico , Glucose/uso terapêutico , Bicarbonato de Sódio/uso terapêutico , Administração Intravenosa , Método Duplo-Cego , Eletrólitos , Glucose/administração & dosagem , Humanos , Injeções Intravenosas , Sódio/sangue , Bicarbonato de Sódio/administração & dosagem , Resultado do Tratamento
4.
Life Sci ; 248: 117468, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32105705

RESUMO

AIMS: Treatment with 5-fluorouracil (5-FU) can cause impairment to adult hippocampal neurogenesis, resulting in cognitive deficits. As melatonin has been shown to enhance memory and hippocampal neurogenesis in animal models, this research investigated the neuroprotective effects of melatonin against spatial memory and hippocampal neurogenesis impairment in 5-fluorouracil (5-FU)-treated rats. MATERIALS AND METHODS: Four-Five weeks old male Spraque-Dawley rats weighing between 180 and 200 g were used. Animals were maintained under standard laboratory conditions with 25 °C and 12 h light/dark cycle. Animal were administered intravenous (i.v.) injections of 5-FU (25 mg/kg) 5 times every 3 days starting on day 9 of the experiment. The rats were divided into preventive, recovery, and throughout groups and co-treated with melatonin (8 mg/kg, i.p.) once daily (at 7.00 pm) for 21 days prior to, after, and throughout 5-FU treatment, respectively. Spatial memory was assessed using a novel object location (NOL) test. Hippocampal neurogenesis was then examined using Ki67, bromodeoxyuridine (BrdU), and doublecortin (DCX) immunohistochemistry staining. KEY FINDINGS: Melatonin administration was able to both protect the subjects from and reverse spatial memory deficits. 5-FU was also found to reduce the generation of hippocampal newborn neurons. However, co-treatment with melatonin ameliorated the reductions in neurogenesis caused by 5-FU. SIGNIFICANCE: These findings suggest that melatonin administration was able to ameliorate the 5-FU-induced spatial memory deficits associated with neurogenesis. The present work will be valuable for patients who suffer memory deficits from 5-FU chemotherapy.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Fluoruracila/antagonistas & inibidores , Melatonina/farmacologia , Transtornos da Memória/tratamento farmacológico , Neurogênese/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Memória Espacial/efeitos dos fármacos , Animais , Antimetabólitos/efeitos adversos , Biomarcadores/metabolismo , Proliferação de Células/efeitos dos fármacos , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Giro Denteado/efeitos dos fármacos , Giro Denteado/metabolismo , Giro Denteado/patologia , Esquema de Medicação , Fluoruracila/efeitos adversos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Injeções Intravenosas , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Neurogênese/genética , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Ratos , Ratos Sprague-Dawley , Memória Espacial/fisiologia
5.
Gynecol Oncol ; 156(1): 13-22, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31708167

RESUMO

BACKGROUND: Improvements in disease free survival for epithelial ovarian, peritoneal or fallopian tube cancer (EOC) will only come with improved primary therapy. Incorporation of poly-ADP-ribose inhibitors (PARPi) in the frontline setting may represent one strategy. This study sought to determine the maximum tolerated and feasible doses of the PARPi veliparib in combination with chemotherapy for EOC. METHODS: A phase I, 3 + 3 dose escalation evaluated dose-limiting toxicities (DLTs) in cycles 1-2. Once <2/6 patients experienced a DLT, that dose level expanded to evaluate feasibility over 4 cycles. This study opened 10/2009 and closed 8/2016. Eligible patients had untreated, stage II-IV EOC. Veliparib was added either continuous (day 1-21) or intermittent (day - 2 to 5) during 6 cycles of chemotherapy. Three chemotherapy backbones were evaluated (2 intravenous (q3week and weekly) and 1 intraperitoneal (IP)) all inclusive of bevacizumab with and as maintenance to 22 cycles. FINDINGS: Dose evaluations for 424 treated patients were available. Regimen 1 (q3 week), continuous (Reg1c) the maximum tolerated dose (MTD) was 250 mg veliparib BID and feasible dose was 150 mg BID. For regimen 1, intermittent (Reg1i) the MTD and feasible dose were 400 and 250 mg BID. For Reg2c (weekly paclitaxel) the MTD and feasible dose were 150 mg BID. For Reg2i the MTD and feasible dose were 250 and 150 mg BID. For Reg3c (IP) the MTD and feasible dose were 150 mg BID and for Reg3i (IP), the MTD and feasible dose were 400 mg and 300 mg BID. INTERPRETATION: The feasible dose for Reg1c, 2c, 2i and 3c was 150 mg po BID. For Reg1i and 3i the dose was pushed to 250 and 300 mg po BID respectively. There is no apparent difference in efficacy between continuous and intermittent dosing indicating that the higher doses achieved in intermittent dosing may not be needed. (NCT00989651). FUNDING: National Cancer Institute.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Epitelial do Ovário/patologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Estudos de Coortes , Relação Dose-Resposta a Droga , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Injeções Intraperitoneais , Injeções Intravenosas , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Neoplasias Peritoneais/patologia , Intervalo Livre de Progressão
6.
Expert Opin Drug Saf ; 19(2): 205-210, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31709853

RESUMO

Objectives: HTX-019 (Cinvanti®) is a novel injectable emulsion formulation of the neurokinin 1 receptor antagonist (RA) aprepitant, approved (as 30-min infusion and 2-min injection) for preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV). This retrospective analysis evaluated the safety of HTX-019 administered by 2-min injection in patients with cancer.Methods: At a single center, HTX-019 was evaluated as a 2-min injection within a guideline-recommended three-drug regimen for CINV prophylaxis in patients receiving highly (HEC) or moderately emetogenic chemotherapy (MEC). Treatment-emergent adverse events (TEAEs) were assessed 0-60 minutes following initiation of HTX-019 administration, focusing on infusion-site adverse events and hypersensitivity reactions.Results: Among 600 patients (78 MEC, 522 HEC), the most common diagnoses were lung (172) and breast (129) cancer. Patients received a 2-min injection of HTX-019, followed by a 5-hydroxytryptamine type 3 RA intravenously (IV) (palonosetron or ondansetron), dexamethasone IV, and chemotherapy regimen (most common was cisplatin-containing) via a central (76%) and peripheral line (24%). No TEAEs occurred within 60 min after start of HTX-019 administration.Conclusion: HTX-019 administered by 2-min injection has a tolerable safety profile in patients with cancer, representing a viable method of HTX-019 administration for CINV prevention.


Assuntos
Antieméticos/administração & dosagem , Aprepitanto/administração & dosagem , Antagonistas do Receptor de Neuroquinina-1/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antieméticos/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Aprepitanto/efeitos adversos , Dexametasona/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Infusões Intravenosas , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/prevenção & controle , Neoplasias/tratamento farmacológico , Antagonistas do Receptor de Neuroquinina-1/efeitos adversos , Ondansetron/administração & dosagem , Palonossetrom/administração & dosagem , Estudos Retrospectivos , Vômito/induzido quimicamente , Vômito/prevenção & controle
7.
Arch Dis Child Fetal Neonatal Ed ; 105(1): 14-17, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31072967

RESUMO

OBJECTIVE: To assess whether oxytocin administered before clamping the umbilical cord modifies the volume of placental transfusion. DESIGN: Randomised controlled trial. METHODS: Mothers of term infants born vigorous by vaginal delivery with informed consent provided in early labour were randomly assigned to oxytocin (10 IU) given intravenously within 15 s of birth (group 1) or after clamping the umbilical cord 3 min after delivery (group 2). Soon after birth, all infants were weighed using a 1 g precision scale and subsequently placed on the mother's abdomen or chest. At 3 min, in both groups, the cord was clamped and cut, and the weight was again obtained. The primary outcome (volume of placental transfusion) was estimated by the difference in weights. RESULTS: 144 patients were included. There were no differences in the primary outcome: infants in group 1 (n=70) gained a mean weight of 85.9 g (SD 48.3), and in group 2 (n=74) 86.7 g (SD 49.6) (p=0.92). No differences were found in secondary outcomes, including newborns' haematocrit and bilirubin concentrations and severe maternal postpartum haemorrhage. On the advice of the Data and Safety Monitoring Committee, the trial was stopped due to futility at 25% of the planned sample size. CONCLUSIONS: When umbilical cord clamping is delayed for 3 min, term newborn infants born vigorous receive a clinically significant placental transfusion which is not modified by the administration of intravenous oxytocin immediately after birth. TRIAL REGISTRATION NUMBER: NCT02618499.


Assuntos
Constrição , Ocitócicos/administração & dosagem , Ocitocina/administração & dosagem , Circulação Placentária , Período Pós-Parto , Cordão Umbilical , Adulto , Bilirrubina/sangue , Peso ao Nascer , Parto Obstétrico , Feminino , Hematócrito , Maternidades , Humanos , Recém-Nascido , Injeções Intravenosas , Masculino , Hemorragia Pós-Parto/prevenção & controle , Gravidez , Fatores de Tempo , Ganho de Peso
8.
Vasc Endovascular Surg ; 54(1): 47-50, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31581906

RESUMO

OBJECTIVES: Cyanoacrylate glue is injected for incompetent great saphenous vein (GSV) treatment 5 cm distal to the saphenofemoral junction (SFJ). Although a few reports have investigated the postprocedural remnant stump length, none have focused on the factors affecting glue extension length and the consequent remnant stump length. METHODS: Seventy-nine patients undergoing cyanoacrylate closure using the VenaSeal system at our clinic between August 2018 and November 2018 were investigated. The GSV diameter was measured just before treatment in the supine position 3 cm distal to the SFJ. Cyanoacrylate glue was injected 5 cm distal to the SFJ. RESULTS: The mean glue extension length was 1.13 ± 1.12 cm. The GSV diameter and glue extension length exhibited a significant inversely proportional relationship (P < .001). More specifically, patients with a GSV diameter ≥0.7 cm had a longer remnant stump length than those with a smaller GSV diameter (P < .001). CONCLUSIONS: An increased GSV diameter is likely associated with a decreased glue extension length and, consequently, a longer remnant stump.


Assuntos
Cianoacrilatos/administração & dosagem , Veia Safena , Adesivos Teciduais/administração & dosagem , Varizes/terapia , Adulto , Cianoacrilatos/efeitos adversos , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Veia Safena/diagnóstico por imagem , Veia Safena/fisiopatologia , Adesivos Teciduais/efeitos adversos , Resultado do Tratamento , Ultrassonografia de Intervenção , Varizes/diagnóstico por imagem , Varizes/fisiopatologia
9.
Eur J Med Chem ; 185: 111823, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31698158

RESUMO

Breast cancer is the most frequently diagnosed malignancy and the second common cause of death in women worldwide. High mortality in breast cancer is frequently associated with metastatic progression rather than the primary tumor itself. It has been recently identified that the CXCR4/CXCL12 axis plays a pivotal role in breast cancer metastasis, especially in directing metastatic cancer cells to CXCL12-riched organs and tissues. Herein, taking the amide-sulfamide as the lead structure, the second-round structural modifications to the sulfamide structure were performed to obtain more active CXCR4 modulators against tumor metastasis. Both in vivo and in vitro experiments illustrated that compound IIIe possessed potent CXCR4 binding affinity, excellent anti-metastatic and anti-angiogenetic activity against breast cancer. More importantly, in a mouse breast cancer lung metastasis model, compound IIIe exerted a significant inhibitory effect on breast cancer metastasis. Taken together, all these positive results demonstrated that developing of CXCR4 modulators is a promising strategy to mediate breast cancer metastasis.


Assuntos
Amidas/farmacologia , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Quimiocina CXCL12/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Experimentais/tratamento farmacológico , Receptores CXCR4/antagonistas & inibidores , Amidas/administração & dosagem , Amidas/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Neoplasias da Mama/patologia , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quimiocina CXCL12/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Injeções Intravenosas , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/patologia , Neoplasias Experimentais/secundário , Receptores CXCR4/metabolismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Cicatrização/efeitos dos fármacos
10.
PLoS Negl Trop Dis ; 13(12): e0007856, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31805052

RESUMO

Cutaneous leishmaniasis (LC) is a complex and variable disease in terms of epidemiology, aetiology, pathology and clinical characteristics. The mainstay of treatment is still pentavalent antimony (Sbv) compounds administered systemically, despite their recognized toxicity. The advantages of antimony intralesional (IL) infiltration are the use of lower doses of Sbv and, therefore, less toxic effects. The objective of this study was to estimate the cost-effectiveness ratio of intralesional meglumine antimoniate therapy (IL-MA) compared with endovenous meglumine antimoniate therapy (EV-MA) for the treatment of CL in the context of the Brazilian National Health System (SUS). An analytical decision model (decision tree) was developed using TreeAge Pro 2018 software. Data from the open-label, uncontrolled phase II clinical trial evaluating IL-MA were used as a reference for posology, efficacy, and adverse event rates (AE). The same premises for the intravenous approach (EV-MA) were extracted from systematic literature reviews. Macro and micro calculations of spending were included in the analysis. The IL-MA and EV-MA strategies had a total cost per patient cured of US$330.81 and US$494.16, respectively. The intralesional approach was dominant, meaning it was more economic and effective than was endovenous therapy. The incremental cost-effectiveness ratio showed that IL-MA could result in savings of US$864.37 for each additional patient cured, confirming that the IL-MA strategy is cost effective in the context of the Brazilian public health scenario.


Assuntos
Antiprotozoários/administração & dosagem , Análise Custo-Benefício , Leishmaniose Cutânea/tratamento farmacológico , Antimoniato de Meglumina/administração & dosagem , Administração Tópica , Adulto , Brasil , Ensaios Clínicos como Assunto , Humanos , Injeções Intravenosas , Pessoa de Meia-Idade , Adulto Jovem
11.
Yakugaku Zasshi ; 139(12): 1539-1546, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31787641

RESUMO

Fullerenes, large spherical molecules composed solely of carbon atoms, have gathered much attention for practical applications that take advantage of their unique spherical structure, physical properties, and biological activities. For example, fullerene C60 can function as a photosensitizer, an antioxidant, a bioimaging agent, and as a gene or drug carrier. However, the practical use of C60 for these potential biomedical applications has been hampered by the fact that it is only sparingly soluble in water. In this review, we focus on the development of hydrophilic C60 nanoparticles, the surface of which is covered by cyclodextrin (CD), and then evaluate its biological activities. C60/CD nanoparticles were stable under physiological conditions, and even under much harsher conditions. The nanoparticles generate reactive oxygen species (ROS) under visible light irradiation. Efficient photodynamic therapy against tumor growth was achieved by the intravenous injection of C60/CD nanoparticles to tumor bearing mice, followed by photoirradiation. In addition, C60(OH)10, which is regarded as a potential candidate for use in scavenging ROS, was also prepared in the form of water soluble nanoparticles. C60(OH)10/CD nanoparticles protect the liver from injury by the suppression of oxidative stress occurring in the mitochondria, for example, by scavenging ROS such as superoxide anion radicals (O2・-), nitric oxide (NO) and peroxynitrite (ONOO-), which act as critical mediators in liver injuries. C60-based nanoparticles represent a potentially promising material for use in the treatment of cancer and oxidative stress-related diseases, and are promising as well in terms of extensive biological applications.


Assuntos
Fulerenos/química , Nanomedicina , Neoplasias/tratamento farmacológico , Animais , Antioxidantes , Carbono/química , Ciclodextrinas , Depuradores de Radicais Livres , Fulerenos/administração & dosagem , Fulerenos/farmacologia , Humanos , Interações Hidrofóbicas e Hidrofílicas , Injeções Intravenosas , Camundongos , Mitocôndrias/metabolismo , Nanopartículas , Estresse Oxidativo/efeitos dos fármacos , Fotoquimioterapia , Espécies Reativas de Oxigênio
12.
J Pediatr Ophthalmol Strabismus ; 56: e68-e72, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31821510

RESUMO

Differentiating true optic nerve edema from pseudo-optic nerve edema is a diagnostic dilemma faced by pediatric ophthalmologists. This case series suggests that oral fluorescein angiography is equivalent to intravenous fluorescein angiography in making this distinction. [J Pediatr Ophthalmol Strabismus. 2019;56:e68-e72.].


Assuntos
Angiofluoresceinografia/métodos , Verde de Indocianina/administração & dosagem , Drusas do Disco Óptico/diagnóstico , Nervo Óptico/patologia , Administração Oral , Adolescente , Criança , Corantes/administração & dosagem , Feminino , Fundo de Olho , Humanos , Injeções Intravenosas , Masculino
13.
J Clin Ethics ; 30(4): 356-359, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31851627

RESUMO

Intravenous drug abusers may incur bloodstream infections, in particular those involving the heart valves, that often require extended courses of antibiotics, commonly on the order of six weeks. Conventional wisdom has dictated that even when patients are sufficiently well to not need ongoing hospitalization, it is unsafe to complete their antibiotic course in any setting other than in a closely supervised facility, even if this is contrary to their wishes. The assumption has been that such patients would be at risk of using their indwelling intravenous catheter for illicit purposes. Recent advances in the care of patients who suffer from addiction disorders suggest that when patients receive state-of-the-art addiction treatment, many may be able to continue their intravenous antibiotic course unsupervised, at home. This represents a departure from the parentalistic model of care of impaired patients who are prone to self-harm, moving towards a model that respects autonomy and trusts patients who are in recovery to continue their care in a manner that is self-beneficial.


Assuntos
Antibacterianos/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Injeções Intravenosas/ética , Transtornos Relacionados ao Uso de Opioides/complicações , Hospitalização , Humanos
14.
Undersea Hyperb Med ; 46(5): 659-663, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31683365

RESUMO

Treatment of idiopathic sensorineural hearing loss (ISSNHL) is problematic due to the unclear etiology of the illness. Corticosteroid is recommended by some papers, and hyperbaric oxygen (HBO2) by others. Recently HBO2 has been shown to be an important therapy for ISSNHL, with an increasing number of studies demonstrating its beneficial results. Recovery from ISSNHL depends on the interval period between onset and treatment, hearing loss severity and audiogram type used to determine damage. Treatment of ISSNHL requires a detailed analysis. In this retrospective study we reviewed data from 56 patients with moderate ISSNHL. These patients were divided into three groups based on different treatments: corticosteroid group; corticosteroid + HBO2 (combination)group; and HBO2-only group. Additionally, all patients received intravenous vasodilator treatment. Hearing levels before and after treatment were compared. All three groups had a similar recovery rate, with an effective rate of more than 50%, and a hearing gain average of 17.38 decibels (dB). HBO2 treatment got a higher recovery rate. The combination therapy, which included corticosteroid and HBO2, did not elevate the recovery rate.


Assuntos
Corticosteroides/uso terapêutico , Perda Auditiva Neurossensorial/terapia , Perda Auditiva Súbita/terapia , Oxigenação Hiperbárica , Vasodilatadores/administração & dosagem , Terapia Combinada/métodos , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Recuperação de Função Fisiológica , Estudos Retrospectivos
15.
N Engl J Med ; 381(19): 1831-1842, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31693806

RESUMO

BACKGROUND: Patients who are treated with targeted temperature management after out-of-hospital cardiac arrest with shockable rhythm are at increased risk for ventilator-associated pneumonia. The benefit of preventive short-term antibiotic therapy has not been shown. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving adult patients (>18 years of age) in intensive care units (ICUs) who were being mechanically ventilated after out-of-hospital cardiac arrest related to initial shockable rhythm and treated with targeted temperature management at 32 to 34°C. Patients with ongoing antibiotic therapy, chronic colonization with multidrug-resistant bacteria, or moribund status were excluded. Either intravenous amoxicillin-clavulanate (at doses of 1 g and 200 mg, respectively) or placebo was administered three times a day for 2 days, starting less than 6 hours after the cardiac arrest. The primary outcome was early ventilator-associated pneumonia (during the first 7 days of hospitalization). An independent adjudication committee determined diagnoses of ventilator-associated pneumonia. RESULTS: A total of 198 patients underwent randomization, and 194 were included in the analysis. After adjudication, 60 cases of ventilator-associated pneumonia were confirmed, including 51 of early ventilator-associated pneumonia. The incidence of early ventilator-associated pneumonia was lower with antibiotic prophylaxis than with placebo (19 patients [19%] vs. 32 [34%]; hazard ratio, 0.53; 95% confidence interval, 0.31 to 0.92; P = 0.03). No significant differences between the antibiotic group and the control group were observed with respect to the incidence of late ventilator-associated pneumonia (4% and 5%, respectively), the number of ventilator-free days (21 days and 19 days), ICU length of stay (5 days and 8 days if patients were discharged and 7 days and 7 days if patients had died), and mortality at day 28 (41% and 37%). At day 7, no increase in resistant bacteria was identified. Serious adverse events did not differ significantly between the two groups. CONCLUSIONS: A 2-day course of antibiotic therapy with amoxicillin-clavulanate in patients receiving a 32-to-34°C targeted temperature management strategy after out-of-hospital cardiac arrest with initial shockable rhythm resulted in a lower incidence of early ventilator-associated pneumonia than placebo. No significant between-group differences were observed for other key clinical variables, such as ventilator-free days and mortality at day 28. (Funded by the French Ministry of Health; ANTHARTIC ClinicalTrials.gov number, NCT02186951.).


Assuntos
Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/uso terapêutico , Parada Cardíaca Extra-Hospitalar/complicações , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Adulto , Idoso , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Antibacterianos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Injeções Intravenosas , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/mortalidade , Pneumonia Associada à Ventilação Mecânica/etiologia , Pneumonia Associada à Ventilação Mecânica/microbiologia , Resultado do Tratamento , Desmame do Respirador
16.
Medicine (Baltimore) ; 98(45): e17940, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702683

RESUMO

Venous air embolism (VAE) can be observed in the right heart system on contrast-enhanced computed tomography (CT), following injection of contrast media with a power injector system. Although most VAEs are mostly asymptomatic, they may result in paradoxical air embolism (PAE).To evaluate whether the incidence of VAE on coronary CT angiography is associated with the process of preparation of the intravenous access route.We retrospectively evaluated 692 coronary CT examinations at 3 institutions. Trained CT nurses placed an intravenous cannula in the forearm. Tubes connected to the cannula were prepared in the following ways: A, using an interposed three-way cock and a 20-mL syringe filled with normal saline to collect air contamination in the tube; B, through direct connection to the power injector system without the interposed 3-way cock; and C, using an interposed three-way cock and a 100-mL normal saline drip infusion bottle system to keep the tube patent. The incidence and location of VAE and preparation of intravenous injection were assessed.The overall incidence of VAE was 55.3% (383/692), most frequently observed in the right atrium (81.5%, 312/383). Its incidence varied significantly across the 3 techniques (A: 21.6% (35/162), B: 63.2% (237/375) and C: 71.6% (111/155); P < .001). No patient demonstrated any symptom associated with VAE.Using a 3-way cock with syringe demonstrated the lowest incidence of VAE on coronary CT angiography. It is thus recommended to reduce potential complication risks related to intravenous contrast media injection.


Assuntos
Angiografia por Tomografia Computadorizada/efeitos adversos , Embolia Aérea/etiologia , Embolia Paradoxal/etiologia , Átrios do Coração/diagnóstico por imagem , Idoso , Meios de Contraste/administração & dosagem , Embolia Aérea/complicações , Embolia Aérea/epidemiologia , Embolia Paradoxal/epidemiologia , Humanos , Injeções Intravenosas/efeitos adversos , Injeções Intravenosas/instrumentação , Injeções Intravenosas/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
17.
Bull Cancer ; 106(12): 1124-1131, 2019 Dec.
Artigo em Francês | MEDLINE | ID: mdl-31759513

RESUMO

INTRODUCTION: Home healthcare can be totally different depending on the route of treatment: intravenous anticancer drugs involve regular contact with the health caregiver while the oral route leaves the patient completely autonomous. This cross-sectional research has a comparative purpose between the representations of disease and treatments, the self-efficacy and the quality of life of patients treated with oral anticancer drugs and those treated by intravenous route. METHODS: The sample include 130 patients with cancer. Seventy-two are treated with intravenous chemotherapy and 48 by oral route. The protocol includes a questionnaire of disease representations (IPQ-r), treatment representations (BMQ), self-efficacy (GSES 10) and quality of life (QLQ-C30). RESULTS: The administration route of anticancer treatment impacts the illness representations with the normalization of cancer. The intravenous route, by its invasive and time-consuming nature, increases difficulties in fulfilling family and professional roles. Moreover, side effects are correlated with the perceived dangerousness of the treatment and self-efficacy. Age and the length of time since the diagnosis affect respectively the understanding of the disease and the cognitive dimension of quality of life. DISCUSSION: More than a difference in form of treatment, the whole pathway of healthcare has to be taken into account since it involves different psychological consequences, in particular about therapeutic choices or in terms of patient support.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias/tratamento farmacológico , Qualidade de Vida , Autoeficácia , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Estudos Transversais , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Neoplasias/psicologia , Autocuidado , Inquéritos e Questionários
19.
Medicine (Baltimore) ; 98(38): e17331, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31568020

RESUMO

RATIONALE: The regimen of the recombinant tissue plasminogen activator (rt-PA) is identical in every case where it is indicated in the treatment of cerebral infarction. We report a case of efficient recanalization of large arterial occlusion after rapid injection of rt-PA. PATIENT CONCERNS: A 78-year-old man was admitted with right-sided hemiplegia and global aphasia that occurred an hour ago. DIAGNOSES: His brain computed tomography (CT) revealed no hemorrhage, suggesting cerebral infarction. INTERVENTIONS: Ten percent of a total rt-PA dose was injected over 1 minute promptly. The remainder of rt-PA was designed to be infused for 60 minutes. Unexpectedly, during the study of CT angiography, administration of rt-PA was completed within 5 minutes. CT angiography showed occlusion from carotid bifurcation to the middle cerebral artery. OUTCOMES: After 2 hours of rt-PA administration, the patient began to regain strength in his right arm and leg. By the next day, he had only mild dysarthria and aphasia. Follow-up CT angiography revealed recanalized internal cervical artery and severe residual stenosis with a plaque. He was discharged without any neurologic symptoms. LESSONS: The infusion protocol of rt-PA administration is established in 1995 and has not changed. Successful recanalization of long segmental large vessel occlusion with only intravenous rt-PA is relatively low. In our case, a high concentration of rt-PA may have influenced the successful dissemination of large thrombus in the whole internal cervical artery. Our case is of significance as it raises the question of unanswered efficacy of diverse injection protocol according to thrombus size and bleeding risk.


Assuntos
Infarto Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Infarto Cerebral/diagnóstico por imagem , Humanos , Injeções Intravenosas/métodos , Masculino , Neuroimagem , Proteínas Recombinantes , Fatores de Tempo , Ativador de Plasminogênio Tecidual/administração & dosagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
Nat Commun ; 10(1): 4520, 2019 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-31586045

RESUMO

Control over the protein corona of nanomaterials allows them to function better. Here, by taking graphene/gold as examples, we comprehensively assessed the association of surface properties with the protein corona. As revealed by in vitro measurements and computations, the interaction between graphene/gold and HSA/IgE was inversely correlated with the hydroxyl group availability, whereas the interaction between that and ApoE was comparatively less relevant. Molecular simulations revealed that the number and the distribution of surface hydroxyl groups could regulate the manner in which nanomaterials interact with proteins. Moreover, we validated that ApoE pre-adsorption before injection enhances the blood circulation of nanomaterials relative to their pristine and IgE-coated counterparts. This benefit can be attributed to the invulnerability of the complementary system provided by ApoE, whose encasement does not increase cytotoxicity. Overall, this study offers a robust yet simple way to create protein corona enriched in dysopsonins to realize better delivery efficacy.


Assuntos
Portadores de Fármacos/química , Nanopartículas/química , Coroa de Proteína/metabolismo , Adsorção , Animais , Apolipoproteínas E/química , Apolipoproteínas E/metabolismo , Linhagem Celular Tumoral/transplante , Modelos Animais de Doenças , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/farmacocinética , Feminino , Ouro/química , Grafite/química , Humanos , Imunoglobulina E/química , Imunoglobulina E/metabolismo , Injeções Intravenosas , Camundongos , Simulação de Dinâmica Molecular , Nanopartículas/metabolismo , Neoplasias/tratamento farmacológico , Proteínas Opsonizantes/química , Ligação Proteica , Coroa de Proteína/química , Estrutura Secundária de Proteína , Células RAW 264.7 , Albumina Sérica Humana/metabolismo , Propriedades de Superfície
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