RESUMO
OBJECTIVE: To assess the clinical implications of cryoanalgesia for pain management in children undergoing minimally invasive repair of pectus excavatum (MIRPE). BACKGROUND: MIRPE entails significant pain management challenges, often requiring high postoperative opioid use. Cryoanalgesia, which blocks pain signals by temporarily ablating intercostal nerves, has been recently utilized as an analgesic adjunct. We hypothesized that the use of cryoanalgesia during MIRPE would decrease postoperative opioid use and length of stay (LOS). MATERIALS AND METHODS: A multicenter retrospective cohort study of 20 US children's hospitals was conducted of children (age below 18 years) undergoing MIRPE from January 1, 2014, to August 1, 2019. Differences in total postoperative, inpatient, oral morphine equivalents per kilogram, and 30-day LOS between patients who received cryoanalgesia versus those who did not were assessed using bivariate and multivariable analysis. P value <0.05 is considered significant. RESULTS: Of 898 patients, 136 (15%) received cryoanalgesia. Groups were similar by age, sex, body mass index, comorbidities, and Haller index. Receipt of cryoanalgesia was associated with lower oral morphine equivalents per kilogram (risk ratio=0.43, 95% confidence interval: 0.33-0.57) and a shorter LOS (risk ratio=0.66, 95% confidence interval: 0.50-0.87). Complications were similar between groups (29.8% vs 22.1, P =0.07), including a similar rate of emergency department visit, readmission, and/or reoperation. CONCLUSIONS: Use of cryoanalgesia during MIRPE appears to be effective in lowering postoperative opioid requirements and LOS without increasing complication rates. With the exception of preoperative gabapentin, other adjuncts appear to increase and/or be ineffective at reducing opioid utilization. Cryoanalgesia should be considered for patients undergoing this surgery.
Assuntos
Tórax em Funil , Transtornos Relacionados ao Uso de Opioides , Criança , Humanos , Adolescente , Analgésicos Opioides/uso terapêutico , Estudos Retrospectivos , Tórax em Funil/cirurgia , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Morfina , Procedimentos Cirúrgicos Minimamente InvasivosRESUMO
Tomato brown rugose fruit virus (ToBRFV) has become a cause of great concern in the global tomato agro-industry since its first report in Israel in 2014. Global tomato production is affected by ToBRFV, and management practices are being evaluated. We tested seed lots from international producers as well as greenhouse substrates and water wells as possible sources of virus contamination. We identified a second introduction of ToBRFV in Mexico by a strain closely resembling isolates from the Netherlands and the Middle East. ToBRFV was detected by RT-PCR in seed coats and epicotyls (from commercial seeds and seedlings obtained from infected tomato plants), indicating a transmission rate of 9%. Virus-like particles (VLPs) were found in wells used for irrigation in greenhouses, but these exhibited low infectivity. These findings suggest that water sources could serve as ToBRFV reservoirs. We evaluated four chemical and six thermal methods for sanitizing substrates, plasticware, and other greenhouse utensils, using detached leaf bioassays in Nicotiana rugosa. The most effective chemical sanitization method was treatment with glutaraldehyde plus quaternary ammonium salts and pentapotassium salts. The most effective heat treatment was at 92°C for 30 minutes, which inactivated the virus. Tomato producers could implement these sanitization methods to control ToBRFV.
Assuntos
Frutas , Solanum lycopersicum , México , Sais , BioensaioRESUMO
BACKGROUND: Colonoscopic screening and surveillance for colorectal cancer could be made safer and more efficient if endoscopists could predict histology without the need to biopsy and perform histopathology on every polyp. Elastic-scattering spectroscopy (ESS), using fiberoptic probes integrated into standard biopsy tools, can assess, both in vivo and in real time, the scattering and absorption properties of tissue related to its underlying pathology. AIMS: The objective of this study was to evaluate prospectively the potential of ESS to predict polyp pathology accurately. METHODS: We obtained ESS measurements from patients undergoing screening/surveillance colonoscopy using an ESS fiberoptic probe integrated into biopsy forceps. The integrated forceps were used for tissue acquisition, following current standards of care, and optical measurement. All measurements were correlated to the index pathology. A machine learning model was then applied to measurements from 367 polyps in 169 patients to prospectively evaluate its predictive performance. RESULTS: The model achieved sensitivity of 0.92, specificity of 0.87, negative predictive value (NPV) of 0.87, and high-confidence rate (HCR) of 0.84 for distinguishing 220 neoplastic polyps from 147 non-neoplastic polyps of all sizes. Among 138 neoplastic and 131 non-neoplastic polyps ≤ 5 mm, the model achieved sensitivity of 0.91, specificity of 0.88, NPV of 0.89, and HCR of 0.83. CONCLUSIONS: Results show that ESS is a viable endoscopic platform for real-time polyp histology, particularly for polyps ≤ 5 mm. ESS is a simple, low-cost, clinically friendly, optical biopsy modality that, when interfaced with minimally obtrusive endoscopic tools, offers an attractive platform for in situ polyp assessment.
Assuntos
Adenocarcinoma/diagnóstico , Pólipos Adenomatosos/diagnóstico , Pólipos do Colo/diagnóstico , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Diagnóstico por Computador/métodos , Análise Espectral/métodos , Adenocarcinoma/patologia , Pólipos Adenomatosos/patologia , Inteligência Artificial , Pólipos do Colo/patologia , Neoplasias Colorretais/patologia , Humanos , Sensibilidade e Especificidade , Análise Espectral/instrumentaçãoRESUMO
PURPOSE: The majority of pediatric patients with choledochal cysts (CDC) are symptomatic prior to undergoing CDC excision. This study investigated the impact of surgical timing of CDC excision on postoperative outcomes among children. METHODS: We performed a retrospective review of 59 patients undergoing open CDC excision with Roux-Y hepaticojejunostomy between 2000 and 2020. Patients were grouped based on whether they underwent an electively scheduled or urgent CDC excision, as defined as CDC excision within the same admission due to CDC-related symptoms. Patient characteristics and perioperative data were compared between the two groups. RESULTS: Patients who underwent an elective surgery were older, had more Todani-type 1 CDC, and had decreased postoperative hospital length of stay and opioid use compared to patients who underwent CDC excision within the same admission due to CDC-related symptoms. No significant differences emerged regarding postoperative complications. Multivariable analysis showed that elective cyst excision (HR = 0.55, p = 0.04; HR = 0.59, p = 0.008) and type 1 CDC (HR = 0.32, p = 0.03; HR = 0.12, p < 0.001) were independently associated with decreased opioid use and postoperative hospital length of stay. CONCLUSIONS: Elective CDC excision is associated with shortened hospital stay and decreased opioid use among children compared to patients who undergo a CDC excision during the same admission for CDC-related symptoms.
Assuntos
Cisto do Colédoco , Laparoscopia , Analgésicos Opioides , Anastomose em-Y de Roux , Criança , Cisto do Colédoco/diagnóstico , Cisto do Colédoco/cirurgia , Humanos , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The spread of multidrug resistant bacteria has become a global concern. One of the most important and emergent classes of multidrug-resistant bacteria is extended-spectrum ß-lactamase-producing bacteria (ESBL-positive = ESBL+). Due to widespread and continuous evolution of ESBL-producing bacteria, they become increasingly resistant to many of the commonly used antibiotics, leading to an increase in the mortality associated with resulting infections. Timely detection of ESBL-producing bacteria and rapid determination of their susceptibility to appropriate antibiotics can reduce the spread of these bacteria and the consequent complications. Routine methods used for the detection of ESBL-producing bacteria are time-consuming, requiring at least 48 h to obtain results. In this study, we evaluated the potential of infrared spectroscopic microscopy, combined with multivariate analysis for rapid detection of ESBL-producing Escherichia coli ( E. coli) isolated from urinary-tract infection (UTI) samples. Our measurements were conducted on 837 samples of uropathogenic E. coli (UPEC), including 268 ESBL+ and 569 ESBL-negative (ESBL-) samples. All samples were obtained from bacterial colonies after 24 h culture (first culture) from midstream patients' urine. Our results revealed that it is possible to detect ESBL-producing bacteria, with a 97% success rate, 99% sensitivity, and 94% specificity for the tested samples, in a time span of few minutes following the first culture.
Assuntos
Raios Infravermelhos , Aprendizado de Máquina , Microscopia , Escherichia coli Uropatogênica/isolamento & purificação , Escherichia coli Uropatogênica/metabolismo , beta-Lactamases/biossíntese , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
BACKGROUND: Studies demonstrating an association between anesthesia and brain cell death (neuroapoptosis) in young animals were performed without accompanying surgery. This study tests the hypothesis that fetal surgery decreases anesthesia-induced neuroapoptosis. MATERIALS AND METHODS: Seventy-day-pregnant ewes received 2% isoflurane for 1 h (low dose [LD]) or 4% for 3 h (high dose [HD]) with or without fetal surgery (S). Unexposed fetuses served as controls (C). Fetal brains were processed for neuroapoptosis using anti-caspase-3 antibodies. Data were analyzed using ANOVA. RESULTS: Twenty-eight fetal sheep were evaluated. Dentate gyrus neuroapoptosis was lower in the HD+S group (13.1 ± 3.76 × 105/mm3) than in the HD (19.1 ± 1.40 × 105/mm3, p = 0.012) and C groups (18.3 ± 3.55 × 105/mm3, p = 0.035). In the pyramidal layer of the hippocampus, neuroapoptosis was lower in the HD+S group (8.11 ± 4.88 × 105/mm3) than in the HD (14.8 ± 2.82 × 105/mm3, p = 0.006) and C groups (14.1 ± 4.54 × 105/mm3, p = 0.019). The LD+S group showed a trend towards a significant decrease in neuroapoptosis in the pyramidal layer (LD+S 7.51 ± 1.48 vs. LD 13.5 ± 1.87 vs. C 14.1 ± 4.54 × 105/mm3, p = 0.07) but not in the dentate gyrus. Fetal surgery did not affect neuroapoptosis in the frontal cortex or endplate. CONCLUSIONS: Fetal surgery decreases isoflurane-induced neuroapoptosis in the dentate gyrus and the pyramidal layer of mid-gestational fetal sheep. Long-term effects of these observations on memory and learning deserve further exploration.
Assuntos
Apoptose , Encéfalo/patologia , Fetoscopia , Isoflurano/efeitos adversos , Ovinos , Animais , Caspase 3/metabolismo , Feminino , Isoflurano/uso terapêutico , GravidezRESUMO
OBJECTIVES: Appendicitis is the most common surgical emergency encountered in the pediatric emergency department (ED). We analyzed the time course of children evaluated for suspected appendicitis in relation to implementation of a risk-stratified ultrasound scoring system and structured reporting template (Appy-Score). METHODS: In July 2013, a 6-level ultrasound (US)-based appendicitis scoring system was developed and implemented. The records of children (age ≤18 years) who underwent limited abdominal US exams for suspected appendicitis at a large academic pediatric ED were reviewed retrospectively. Time periods evaluated were from January 1 to April 1, 2013 (before implementation of the US scoring system, "PRE") and July 1 to October 1, 2013 (after implementation of the US scoring system, "POST"). Times are presented as medians with interquartile range. RESULTS: A total of 926 children were included (median age, 9.5 years [range, 0.1-18 years]; 49% female). Four hundred eighty-one patients were evaluated PRE and 445 POST. When comparing the 2 groups, there were no differences in the PRE and POST periods with regard to time from US ordered to first read (102 vs 112 minutes, P = 0.30), US ordered to disposition (215 vs 208 minutes, P = 0.40) and operating room posting (121 vs 122 minutes, P = 0.59), and overall ED stay (329 vs 333 minutes, P = 0.39). CONCLUSIONS: The development of a radiographic appendicitis score, although allowing for a standardized reporting method, did not significantly alter the ED process flow for evaluation of appendicitis. This reflects the complexities in ED throughput and reveals the need for additional factors to change to improve patient flow.
Assuntos
Apendicite/diagnóstico por imagem , Serviço Hospitalar de Emergência/estatística & dados numéricos , Gerenciamento do Tempo/métodos , Ultrassonografia/métodos , Adolescente , Apendicectomia , Apendicite/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Medição de Risco/métodosRESUMO
Onion is one of the oldest and most consumed crops in the world. Its quality deteriorates gradually during prolonged storage. In the present study, white onions of the variety "Sierra Blanca" were stored in a controlled atmosphere (CA) for 7 months. The color, total pungency, microbiological load and total carbohydrates were evaluated. Three treatments were applied: control treatment (CT), regular atmosphere at 2.5 °C without controlled relative humidity (RH); (T1)1% O2 + 1% CO2 at 2.5 °C and 60-75% RH and (T2)3% O2 + 5% CO2 at 2.5 °C and 60-75% RH. The statistical analysis showed a significant effect of the treatments and storage time in most of the variables analyzed. The CA managed to preserve the quality of the onion during the storage period while the control bulbs exhibited greater deterioration. These increased 2.9 times their level of pungency, had a higher microbial load and showed a very noticeable color change at the end of storage with respect to freshly harvested onions and those stored in a CA. They had a more yellow-green coloration. Both CA treatments were effective in preserving onion quality, but a more positive effect for T1 than T2 was observed on most of the parameters evaluated.
RESUMO
Bacterial pathogens are one of the primary causes of human morbidity worldwide. Historically, antibiotics have been highly effective against most bacterial pathogens; however, the increasing resistance of bacteria to a broad spectrum of commonly used antibiotics has become a global health-care problem. Early and rapid determination of bacterial susceptibility to antibiotics has become essential in many clinical settings and, sometimes, can save lives. Currently classical procedures require at least 48 h for determining bacterial susceptibility, which can constitute a life-threatening delay for effective treatment. Infrared (IR) microscopy is a rapid and inexpensive technique, which has been used successfully for the detection and identification of various biological samples; nonetheless, its true potential in routine clinical diagnosis has not yet been established. In this study, we evaluated the potential of this technique for rapid identification of bacterial susceptibility to specific antibiotics based on the IR spectra of the bacteria. IR spectroscopy was conducted on bacterial colonies, obtained after 24 h culture from patients' samples. An IR microscope was utilized, and a computational classification method was developed to analyze the IR spectra by novel pattern-recognition and statistical tools, to determine E. coli susceptibility within a few minutes to different antibiotics, gentamicin, ceftazidime, nitrofurantoin, nalidixic acid, ofloxacin. Our results show that it was possible to classify the tested bacteria into sensitive and resistant types, with success rates as high as 85% for a number of examined antibiotics. These promising results open the potential of this technique for faster determination of bacterial susceptibility to certain antibiotics.
Assuntos
Resistência Microbiana a Medicamentos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Microscopia/métodos , Espectrofotometria Infravermelho/métodos , Antibacterianos/farmacologia , Ceftazidima/farmacologia , Humanos , Análise Multivariada , Urina/microbiologiaRESUMO
We aimed to determine clinical outcomes 1 year after successful chronic total occlusion (CTO) PCI and, in particular, whether use of dissection and re-entry strategies affects clinical outcomes. Hybrid approaches have increased the procedural success of CTO percutaneous coronary intervention (PCI) but longer-term outcomes are unknown, particularly in relation to dissection and re-entry techniques. Data were collected for consecutive CTO PCIs performed by hybrid-trained operators from 7 United Kingdom (UK) centres between 2012 and 2014. The primary endpoint (death, myocardial infarction, unplanned target vessel revascularization) was measured at 12 months along with angina status. One-year follow up data were available for 96% of successful cases (n = 805). In total, 85% of patients had a CCS angina class of 2-4 prior to CTO PCI. Final successful procedural strategy was antegrade wire escalation 48%; antegrade dissection and re-entry (ADR) 21%; retrograde wire escalation 5%; retrograde dissection and re-entry (RDR) 26%. Overall, 47% of CTOs were recanalized using dissection and re-entry strategies. During a mean follow up of 11.5 ± 3.8 months, the primary endpoint occurred in 8.6% (n = 69) of patients (10.3% (n = 39/375) in DART group and 7.0% (n = 30/430) in wire-based cases). The majority of patients (88%) had no or minimal angina (CCS class 0 or 1). ADR and RDR were used more frequently in more complex cases with greater disease burden, however, the only independent predictor of the primary endpoint was lesion length. CTO PCI in complex lesions using the hybrid approach is safe, effective and has a low one-year adverse event rate. The method used to recanalize arteries was not associated with adverse outcomes. © 2017 Wiley Periodicals, Inc.
Assuntos
Angina Pectoris/terapia , Oclusão Coronária/terapia , Intervenção Coronária Percutânea/métodos , Idoso , Angina Pectoris/diagnóstico por imagem , Angina Pectoris/mortalidade , Distribuição de Qui-Quadrado , Doença Crônica , Angiografia Coronária , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/etiologia , Razão de Chances , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/mortalidade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento , Reino UnidoRESUMO
The cell-penetrating trans-activator of transcription (TAT) is a cationic peptide derived from human immunodeficiency virus-1. It has been used to facilitate macromolecule delivery to various cell types. This cationic peptide is capable of crossing the blood-brain barrier and therefore might be useful for enhancing the delivery of drugs that target brain tumors. Here we test the efficiency with which relatively small (20 nm) micelles can be delivered by an intra-arterial route specifically to gliomas. Utilizing the well-established method of flow-arrest intra-arterial injection we compared the degree of brain tumor deposition of cationic TAT-decorated micelles versus neutral micelles. Our in vivo and post-mortem analyses confirm glioma-specific deposition of both TAT-decorated and neutral micelles. Increased tumor deposition conferred by the positive charge on the TAT-decorated micelles was modest. Computational modeling suggested a decreased relevance of particle charge at the small sizes tested but not for larger particles. We conclude that continued optimization of micelles may represent a viable strategy for targeting brain tumors after intra-arterial injection. Particle size and charge are important to consider during the directed development of nanoparticles for intra-arterial delivery to brain tumors.
Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Produtos do Gene tat , Glioma/tratamento farmacológico , Micelas , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Neoplasias Encefálicas/metabolismo , Cátions , Linhagem Celular Tumoral , Simulação por Computador , Relação Dose-Resposta a Droga , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Produtos do Gene tat/química , Glioma/metabolismo , Hemodinâmica , Concentração de Íons de Hidrogênio , Injeções Intra-Arteriais , Modelos Biológicos , Nanopartículas/administração & dosagem , Nanopartículas/química , Tamanho da Partícula , RatosRESUMO
Bacterial resistance to antibiotics is becoming a global health-care problem. Bacteria are involved in many diseases, and antibiotics have been the most effective treatment for them. It is essential to treat an infection with an antibiotic to which the infecting bacteria is sensitive; otherwise, the treatment is not effective and may lead to life-threatening progression of disease. Classical microbiology methods that are used for determination of bacterial susceptibility to antibiotics are time consuming, accounting for problematic delays in the administration of appropriate drugs. Infrared-absorption microscopy is a sensitive and rapid method, enabling the acquisition of biochemical information from cells at the molecular level. The combination of Fourier transform infrared (FTIR) microscopy with new statistical classification methods for spectral analysis has become a powerful technique, with the ability to detect structural molecular changes associated with resistivity of bacteria to antibiotics. It was possible to differentiate between isolates of Escherichia (E.) coli that were sensitive or resistant to different antibiotics with good accuracy. The objective computational classifier, based on infrared absorption spectra, is highly sensitive to the subtle infrared spectral changes that correlate with molecular changes associated with resistivity. These changes enable differentiating between the resistant and sensitive E. coli isolates within a few minutes, following the initial culture. This study provides proof-of-concept evidence for the translational potential of this spectroscopic technique in the clinical management of bacterial infections, by characterizing and classifying antibiotic resistance in a much shorter time than possible with current standard laboratory methods.
Assuntos
Farmacorresistência Bacteriana , Escherichia coli/isolamento & purificação , Análise Multivariada , Espectroscopia de Infravermelho com Transformada de Fourier , Escherichia coli/efeitos dos fármacosRESUMO
Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints. AT9283 caused tolerable toxicity, but failed to show clinical responses. Future trials should be based on robust preclinical data that provide an indication of which patients may benefit from the experimental agent, and recruitment should be improved through international collaborations and early combination with established treatment strategies.
Assuntos
Aurora Quinases/antagonistas & inibidores , Benzimidazóis/administração & dosagem , Benzimidazóis/farmacocinética , Leucemia/tratamento farmacológico , Proteínas de Neoplasias/antagonistas & inibidores , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacocinética , Ureia/análogos & derivados , Doença Aguda , Adolescente , Benzimidazóis/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leucemia/enzimologia , Masculino , Dose Máxima Tolerável , Inibidores de Proteínas Quinases/efeitos adversos , Ureia/administração & dosagem , Ureia/efeitos adversos , Ureia/farmacocinéticaRESUMO
BACKGROUND: Advances in surgery and technology have resulted in increased in-utero procedures. However, the effect of anesthesia on the fetal brain is not fully known. The inhalational anesthetic agent, isoflurane, other gamma amino butyric acid agonists (benzodiazepines, barbiturates, propofol, other inhalation anesthetics), and N-methyl D aspartate antagonists, eg, ketamine, have been shown to induce neuroapoptosis. The ovine model has been used extensively to study maternal-fetal physiologic interactions and to investigate different surgical interventions on the fetus. OBJECTIVE: The purpose of this study was to determine effects of different doses and duration of isoflurane on neuroapoptosis in midgestation fetal sheep. We hypothesized that repeated anesthetic exposure and high concentrations of isoflurane would result in increased neuroapoptosis. STUDY DESIGN: Time-dated, pregnant sheep at 70 days gestation (term 145 days) received either isoflurane 2% × 1 hour, 4% × 3 hours, or 2% × 1 hour every other day for 3 exposures (repeated exposure group). Euthanasia occurred following anesthetic exposure and fetal brains were processed. Neuroapoptosis was detected by immunohistochemistry using anticaspase-3 antibodies. Fetuses unexposed to anesthesia served as controls. Another midgestation group with repeated 2% isoflurane exposure was examined at day 130 (long-term group) and neuronal cell density compared to age-matched controls. Representative sections of the brain were analyzed using Aperio Digital imaging (Leica Microsystems Inc, Buffalo Grove, IL). Data, reported by number of neurons per cubic millimeter of brain tissue are presented as means and SEM. Data were analyzed using the Mann-Whitney U and Kruskal-Wallis tests as appropriate. RESULTS: A total of 34 fetuses were studied. There was no significant difference in neuroapoptosis observed in fetuses exposed to 2% isoflurane for 1 hour or 4% isoflurane for 3 hours. Increased neuroapoptosis was observed in the frontal cortex following repeated 2% isoflurane exposure compared to controls (1.57 ± 0.22 × 10(6)/mm(3) vs 1.01 ± 0.44 × 10(6)/mm(3), P = .02). Fetuses at 70 days gestation with repeated exposure demonstrated decreased frontal cortex neurons at day 130 when compared to age-matched controls (2.42 ± 0.3 × 10(5)/mm(3) vs 7.32 ± 0.4 × 10(5)/mm(3), P = .02). No significant difference in neuroapoptosis was observed between the repeated exposure group and controls in the hippocampus, cerebellum, or basal ganglia. CONCLUSION: Repeated isoflurane exposure in midgestation sheep resulted in increased frontal cortex neuroapoptosis. This persisted into late gestation as decreased neuronal cell density. While animal studies should be extrapolated to human beings with caution, our findings suggest that the number of anesthetic/sedative exposures should be considered when contemplating the risks and benefits of fetal intervention as certain fetal therapies may need to be repeated.
Assuntos
Anestésicos Inalatórios/administração & dosagem , Apoptose , Encéfalo/patologia , Isoflurano/administração & dosagem , Troca Materno-Fetal , Animais , Contagem de Células , Relação Dose-Resposta a Droga , Feminino , Lobo Frontal/patologia , Imuno-Histoquímica , Neurônios/patologia , Gravidez , Carneiro DomésticoRESUMO
The relative abundance of anionic lipids on the surface of endothelia and on glioma cells suggests a workable strategy for selective drug delivery by utilizing cationic nanoparticles. Furthermore, the extracellular pH of gliomas is relatively acidic suggesting that tumor selectivity could be further enhanced if nanoparticles can be designed to cationize in such an environment. With these motivating hypotheses the objective of this study was to determine whether nanoparticulate (20 nm) micelles could be designed to improve their deposition within gliomas in an animal model. To test this, we performed intra-arterial injection of micelles labeled with an optically quantifiable dye. We observed significantly greater deposition (end-tissue concentration) of cationizable micelles as compared to non-ionizable micelles in the ipsilateral hemisphere of normal brains. More importantly, we noted enhanced deposition of cationizable as compared to non-ionizable micelles in glioma tissue as judged by semiquantitative fluorescence analysis. Micelles were generally able to penetrate to the core of the gliomas tested. Thus we conclude that cationizable micelles may be constructed as vehicles for facilitating glioma-selective delivery of compounds after intraarterial injection.
Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Glioma/tratamento farmacológico , Micelas , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/metabolismo , Cátions/metabolismo , Corantes Fluorescentes , Glioma/diagnóstico por imagem , Glioma/metabolismo , Injeções Intra-Arteriais , Transplante de Neoplasias , Imagem Óptica , Polietilenoglicóis , Ratos Endogâmicos F344 , Ratos Sprague-Dawley , Análise EspectralRESUMO
Mitoxantrone is a highly cytotoxic antineoplastic drug, however, its poor penetration of the blood-brain barrier has limited its role in the treatment of brain cancers. We hypothesize that intra-arterial (IA) delivery of mitoxantrone may enhance its capacity for regional brain deposition thus expanding its potential as a brain tumor therapy agent. In this study we assessed the dose-response characteristics as well as the feasibility and safety of mitoxantrone delivery to the brain and specifically to gliomas in a rodent model. We show that delivery optimization utilizing the technique of intra-arterial transient cerebral hypoperfusion (IA-TCH) facilitates achieving the highest peak- and end- brain drug concentrations as compared to intravenous and IA delivery without hypoperfusion. Additionally, we observed significant tumor-specific uptake of mitoxantrone when delivered by the IA-TCH method. No untoward effects of IA-TCH delivery of mitoxantrone were observed. The IA-TCH method is shown to be a safely tolerated and feasible strategy for delivering mitoxantrone to tumors in the glioma model tested. Additional investigation is warranted to determine if IA-TCH delivery of mitoxantrone produces clinically relevant benefit.
Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Mitoxantrona/administração & dosagem , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Estudos de Viabilidade , Feminino , Humanos , Infusões Intra-Arteriais , Masculino , Ratos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: Malnutrition is common among children with complex heart disease (CHD). Feeding gastrostomies are often used to improve the nutritional status of such patients. Our purpose was to evaluate a cohort of children with CHD following open Stamm gastrostomy without fundoplication. METHODS: We reviewed all CHD patients who underwent feeding gastrostomy placement from 1/1/2004 to 4/7/2015. Demographic data, cardiac diagnoses, operative details, post-operative complications, and the need for GJ feeding and fundoplication were examined. RESULTS: Open Stamm gastrostomy was performed in 111 patients. Median age at surgery was 37 weeks (3 weeks-13.7 years); average weight was 5.3 ± 4.9 kg. Thirty-four patients (30 %) experienced a total of 37 minor complications, including tube dislodgement after stoma maturation (20), superficial surgical site infection (13), mechanical failure (3), and bleeding (1). Three patients experienced a major complication (need for return to the OR or peri-operative death <30 days). Three patients required a subsequent fundoplication. Fifty-six surviving patients (62 %) continue gastrostomy feeds, of which 7 (13 %) patients require GJ feeds. CONCLUSION: Children with CHD tolerate an open Stamm gastrostomy well with minimal major complications. These results support very selective use of fundoplication in infants and children with CHD who require a feeding gastrostomy.
Assuntos
Nutrição Enteral/métodos , Fundoplicatura , Refluxo Gastroesofágico/complicações , Gastrostomia/métodos , Cardiopatias/complicações , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: Elastic-scattering spectroscopy (ESS) can assess in vivo and in real-time the scattering and absorption properties of tissue related to underlying pathologies. OBJECTIVES: To evaluate the potential of ESS for differentiating neoplastic from non-neoplastic polyps during colonoscopy. DESIGN: Pilot study, retrospective data analysis. SETTING: Academic practice. PATIENTS: A total of 83 patients undergoing screening/surveillance colonoscopy. INTERVENTIONS: ESS spectra of 218 polyps (133 non-neoplastic, 85 neoplastic) were acquired during colonoscopy. Spectral data were correlated with the classification of biopsy samples by 3 GI pathologists. High-dimensional methods were used to design diagnostic algorithms. MAIN OUTCOME MEASUREMENTS: Diagnostic performance of ESS. RESULTS: Analysis of spectra from polyps of all sizes (N = 218) resulted in a sensitivity of 91.5%, specificity of 92.2%, and accuracy of 91.9% with a high-confidence rate of 90.4%. Restricting analysis to polyps smaller than 1 cm (n = 179) resulted in a sensitivity of 87.0%, specificity of 92.1%, and accuracy of 90.6% with a high-confidence rate of 89.3%. Analysis of polyps 5 mm or smaller (n = 157) resulted in a sensitivity of 86.8%, specificity of 91.2%, and accuracy of 90.1% with a high-confidence rate of 89.8%. LIMITATIONS: Sample size, retrospective validation used to obtain performance estimates. CONCLUSION: Results indicate that ESS permits accurate, real-time classification of polyps as neoplastic or non-neoplastic. ESS is a simple, low cost, clinically robust method with minimal impact on procedure flow, especially when integrated into standard endoscopic biopsy tools. Performance on polyps 5 mm or smaller indicates that ESS may, in theory, achieve Preservation and Incorporation of Valuable Endoscopic Innovations performance thresholds. ESS may one day prove to be a useful tool used in endoscopic screening and surveillance of colorectal cancer.
Assuntos
Adenocarcinoma/patologia , Adenoma/patologia , Neoplasias do Colo/patologia , Pólipos do Colo/patologia , Colonoscopia/métodos , Análise Espectral/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Colonoscopia/instrumentação , Técnicas de Apoio para a Decisão , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Sensibilidade e Especificidade , Análise Espectral/instrumentaçãoRESUMO
BACKGROUND: The purpose of this study was to evaluate our experience with pentalogy of Cantrell and the various embryologic variants. MATERIALS AND METHODS: Patient charts and diagnostic imaging studies of all fetuses evaluated at Texas Children's Fetal Center for pentalogy of Cantrell between April 2004 and June 2014 were reviewed retrospectively. Data collected from patient charts included demographic information, clinical presentation, fetal and postnatal imaging findings, operative treatment, pathologic evaluation, and outcomes. RESULTS: There were 10 patients who presented with embryologic variants of pentalogy of Cantrell over a 6-y period. Two cases displayed the full range of embryologic defects observed, and eight cases exhibited variants of the classic pentalogy. Sternal and pericardial defects were each present in 40% of patients. Additional anomalies present included pulmonary hypoplasia, pulmonary artery stenosis, and chromosomal abnormalities. Four patients presented with diaphragmatic defects but no defect in the pericardium, and one patient presented with a defective pericardium but no associated diaphragmatic defect, suggesting highly specific losses of somatic mesoderm during embryologic development. One patient was lost to follow-up, and a second patient underwent termination of pregnancy. Five of the remaining eight patients survived, one of which had the full range of embryologic defects and now attends preschool but requires speech and occupational therapy. The remaining surviving patients have developed without serious sequelae. CONCLUSIONS: This report highlights the spectrum of anomalies observed in the pentalogy of Cantrell and demonstrates that these fetuses can survive but with substantial morbidity.