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1.
Paediatr Anaesth ; 33(1): 46-51, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36264219

RESUMO

BACKGROUND: Acetaminophen is routinely used for perioperative analgesia in children undergoing major surgical procedures. There are few estimates of acetaminophen pharmacokinetic parameters in children with congenital heart disease, especially those with cyanotic heart disease. AIMS: The current study prospectively investigated differences in acetaminophen pharmacokinetics following surgery using cardiopulmonary bypass in children with cyanotic and acyanotic congenital heart disease. METHODS: Children (2-6 years, 9-23 kg) presenting for median sternotomy for Fontan palliation (cyanotic patients) or two ventricle surgical repair (acyanotic patients) were eligible for inclusion. A single intravenous dose of acetaminophen (15 mg/kg) was administered at the start of sternal closure after separation from cardiopulmonary bypass. The time-course of acetaminophen concentrations were described using non-linear mixed effects models. One and two-compartment disposition models with first-order elimination were tested. Pharmacokinetic parameter estimates were scaled using allometry and standardized to a 70 kg person. RESULTS: There were 208 acetaminophen concentrations assayed from 30 children, 15 with cyanotic, and 15 with acyanotic heart disease. A 2-compartment model best described acetaminophen PK. Parameter estimates (population parameter variability, PPV%; 95% confidence interval, CI) were clearance CL 15.3 L.h-1.70 kg-1 (22.2%; 13.8-16.7), intercompartment clearance Q 45.4 L.h-1.70 kg-1 (22.4%; 25.2-61.9), central volume of distribution V1 33.5 L.70 kg-1 (23.2%; 25.9-38.8), peripheral volume of distribution V2 32.1 L.70 kg-1 (21.7%; 25.9-38.8). Neither clearance nor volume parameters differed between cyanotic and acyanotic patients. CONCLUSIONS: Acetaminophen pharmacokinetics were characterized using a 2-compartment model with first-order elimination following cardiac bypass surgery in children. Population pharmacokinetic parameter estimates were similar to other studies in children. No differences were detected between patients with cyanotic and acyanotic heart disease.


Assuntos
Acetaminofen , Cardiopatias Congênitas , Criança , Humanos , Cardiopatias Congênitas/cirurgia
2.
J Arthroplasty ; 38(5): 820-823, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36309144

RESUMO

BACKGROUND: With respect to survivorship following total knee arthroplasty (TKA), joint registries consistently demonstrate higher revision rates for both genders in those aged less than 55 years. The present study analyzed the survivorship of 500 cementless TKAs performed in this age group in a high-volume primary joint unit where cementless TKA has traditionally been used for the majority of patients. METHODS: This was a retrospective review of 500 consecutive TKAs performed in patients aged less than 55 years between March 1994 and April 2017. The primary outcome measures for the study were survivorship and all-cause revisions. Secondary outcome measures included nonrevision procedures, clinical, functional, and radiological outcomes. RESULTS: An all-cause survival rate of 98.4% and an aseptic survival rate of 99.2% at a median time of 10.7 years (interquartile range 7.3-14.9, range 0.2-27.7) were found. Four patents were revised for infection, 2 for stiffness, 1 for aseptic loosening of the tibial component, and 1 for a patella that was resurfaced for anterior knee pain. Thirty four patients (6.8%) had a nonrevision procedure with manipulation under anesthetic accounting for 27. On a multivariate analysis, preoperative range of motion and female gender were negatively associated with postoperative range of motion (P < .001 and P = .003, respectively). Sixty seven patients (17.3%) had radioluscent lines and on a multivariate analysis, there were no significant predictors of radiolucent lines. CONCLUSION: Cementless TKA in the young patient can achieve excellent clinical and functional outcomes. At a median of 10.7 years, aseptic revision rates are exceptionally low at 0.8% for the entire cohort.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Artroplastia do Joelho/métodos , Sobrevivência , Resultado do Tratamento , Articulação do Joelho/cirurgia , Reoperação , Falha de Prótese
3.
Clin Anat ; 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37926562

RESUMO

Multipartite patella is an anatomical variant classified by the fragmentation of the main patellar body. The cause of this variant is due to failure in fusion of the patellar ossification centers. It is commonly misdiagnosed as a fracture of the patella in clinical practice, leading to unnecessary treatment measures. The aim of this review is to provide an overview of the development and classification of this variation, diagnostic imaging techniques, and assess the optimal management technique for the symptomatic patient. Multiple radiographic methods are used to identify this variant, with recent studies highlighting high sensitivity rates for nonradiative methods (ultrasound). In terms of symptomatic management, accessory fragment excision and vastus lateralis release provide the greatest alleviation of symptoms, with screw fixation being less favorable.

4.
J Surg Res ; 234: 184-189, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30527472

RESUMO

BACKGROUND: Cardiac risk factors pose challenges in pediatric posterior spinal fusion (PSF). Differences in risk according to etiology of cardiac disease are unclear. We investigated outcomes of PSF according to presence of congenital heart defect compared to cardiomyopathy. METHODS: Elective PSF for idiopathic scoliosis in patients aged 0-18 y was identified in the 2012-2015 National Surgical Quality Improvement Program-Pediatric. Cardiac risk factors were classified as: no cardiac risk factors or minor cardiac risk factors without congenital heart defect; minor cardiac risk factors because of congenital heart defect; major cardiac risk factors because of congenital heart defect; major cardiac risk factors because of cardiomyopathy. Multivariable logistic regression compared surgical site infection, wound dehiscence, hospital length of stay ≥30 d, and unplanned readmission across these categories. RESULTS: The analysis included 5395 girls and 1691 boys, aged 14 ± 2 y. Among these, 140 patients had minor cardiac risk factors because of congenital heart defect, 144 had major cardiac risk factors because of congenital heart defect, and 20 had major cardiac risk factors because of cardiomyopathy. Rates of any complication were significantly higher among patients with cardiomyopathy (40%) compared to patients with major cardiac risk factors because of congenital heart defect (10%), minor cardiac risk factors because of congenital heart defect, or other minor or no cardiac risk factors (5%; chi-square P < 0.001). In multivariable analysis of 6829 patients, cardiomyopathy predicted greater odds of unplanned readmission compared to no or minor cardiac risk factors (OR = 5.9; 95% CI: 1.8, 19.7; P = 0.004) and compared to major cardiac risk factors because of congenital heart defect (OR = 4.5; 95% CI: 1.1, 17.6; P = 0.032). CONCLUSIONS: Cardiomyopathy is a rare but significant risk factor for complications after pediatric PSF, whereas congenital heart defects did not independently contribute to risk of complications after this procedure.


Assuntos
Cardiomiopatias/complicações , Cardiopatias Congênitas/complicações , Complicações Pós-Operatórias/etiologia , Escoliose/cirurgia , Fusão Vertebral , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Complicações Pós-Operatórias/epidemiologia , Sistema de Registros , Fatores de Risco , Escoliose/complicações , Resultado do Tratamento
5.
J Surg Res ; 232: 298-307, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30463733

RESUMO

BACKGROUND: As management of congenital heart disease (CHD) improves, children with CHD increasingly present for noncardiac surgery. Prior studies report conflicting results on the association between CHD and adverse outcomes in noncardiac surgery. Studies reporting no such association predominantly analyze older children and adolescents. We evaluated whether the association between CHD and adverse surgical outcomes was attenuated by increased age. METHODS: Patients aged 0-17 y, undergoing elective noncardiac surgery, were identified in the National Surgical Quality Improvement Program-Pediatric registry. CHD status was classified as none, minor, major, or severe. Multivariable logistic regression evaluated the association of CHD status with the occurrence of any postoperative complication for groups defined by quintiles of patient age (<1, 1-3, 4-8, 9-13, and 14-17 y). Specific complications included cardiac arrest, reintubation, infection, renal failure, neurological complication, thromboembolic complication, reoperation, 30-d unplanned revisit, 30-d prolonged hospital stay, and mortality. RESULTS: The analysis included 131,164 children, of whom 6420 had minor CHD, 3825 had major CHD, and 963 had severe CHD. The overall rate of complications was 9%. In multivariable analysis, children <1 y old had greater risk of postoperative complications if they had minor (odds ratio [OR] = 1.97; 95% confidence interval [CI]: 1.70, 2.20; P < 0.001), major (OR = 2.58; 95% CI: 2.28, 2.91; P < 0.001), or severe CHD (OR = 4.37; 95% CI: 3.45, 5.54; P < 0.001). In older age groups, however, the presence of CHD was not independently associated with postoperative complications. CONCLUSIONS: In pediatric noncardiac surgery, an independent association of CHD with postoperative complications was only evident among children <1 y old.


Assuntos
Cardiopatias Congênitas/complicações , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Mortalidade Hospitalar , Humanos , Lactente , Recém-Nascido , Tempo de Internação/estatística & dados numéricos , Masculino , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/etiologia , Reoperação/estatística & dados numéricos , Medição de Risco , Análise de Sobrevida , Taxa de Sobrevida
6.
J Pediatr ; 188: 82-86, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28690004

RESUMO

OBJECTIVE: To describe the change in health insurance after heart transplantation among adolescents, and characterize the implications of this change for long-term transplant outcomes. STUDY DESIGN: Patients age 15-18 years receiving first-time heart transplantation between 1999 and 2011 were identified in the United Network for Organ Sharing registry and included in the analysis if they survived at least 5 years. The primary exposure was change or continuity of health insurance coverage between the time of transplant and the 5-year follow-up. Cox proportional hazards models were used to determine the association between insurance status change and long-term (>5 years) patient and graft survival. RESULTS: The analysis included 366 patients (age 16 ± 1 years at transplant), of whom 205 (56%) had continuous private insurance; 96 (26%) had continuous public insurance; and 65 (18%) had a change in insurance status. In stepwise multivariable Cox regression, change in insurance status was associated with greater mortality hazard, compared with continuous private insurance (hazard ratio = 1.9; 95% CI: 1.1, 3.2; P = .016), whereas long-term patient and graft survival did not differ between patients with continuous public and continuous private insurance. CONCLUSIONS: Continuity of insurance coverage is associated with improved long-term clinical outcomes among adolescent heart transplant recipients who survive into adulthood.


Assuntos
Transplante de Coração/economia , Cobertura do Seguro/estatística & dados numéricos , Seguro Saúde/estatística & dados numéricos , Adolescente , Criança , Feminino , Seguimentos , Transplante de Coração/estatística & dados numéricos , Humanos , Masculino , Modelos de Riscos Proporcionais , Sistema de Registros , Análise de Sobrevida , Sobreviventes , Adulto Jovem
7.
Paediatr Anaesth ; 27(4): 370-376, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28181359

RESUMO

BACKGROUND: Mucopolysaccharidosis type III is a progressive disease with worsening airway, pulmonary, and cardiac involvement that may complicate anesthetic care. AIM: To prospectively evaluate the incidence of airway issues and complications during magnetic resonance imaging (MRI) and lumbar puncture (LP) during general anesthesia with a native airway for patients with mucopolysaccharidosis type III. METHOD: The study was a part of the natural history study. Anesthesia was induced with sevoflurane, which was discontinued after intravenous access was obtained. General anesthesia with a native airway was provided by dexmedetomidine and propofol. Dexmedetomidine (0.5 µg·kg-1 ) was administered over 5 min followed by a continuous infusion at 0.5 µg·kg-1 ·h-1 . A continuous infusion of propofol was started at 150 µg·kg-1 ·min-1 . A bolus dose of propofol (1 mg·kg-1 ) was administered and the propofol infusion was increased as needed. Airway management and vital signs were recorded for the entire procedure until discharge. RESULTS: Twenty-five patients (6.9 ± 3.1 years) received total of 43 MRI and LP procedures in the cohort. No patient failed sedation. Although mask induction with sevoflurane was not clinically problematic, upper airway obstruction was noted during 14 procedures (33%). This required the application of continuous positive airway pressure, temporary oral airway placement, jaw thrust, or shoulder roll. Airway dynamics improved once the anesthesia was transitioned to intravenous anesthetic agents. Although a small shoulder roll was needed to improve airway patency for 11 cases (26%), a large shoulder roll tended to make the upper airway obstruction worse. Oxygen desaturation (≤90%) was noted during MRI in three cases (7%). CONCLUSION: A combination of dexmedetomidine and propofol provided effective general anesthesia with a native airway during the procedures. Although upper airway obstruction was noted, it resolved with simple airway maneuvers without further airway intervention.


Assuntos
Manuseio das Vias Aéreas/métodos , Anestesia Geral/métodos , Mucopolissacaridose III/complicações , Posicionamento do Paciente/métodos , Adolescente , Anestésicos Intravenosos , Criança , Pré-Escolar , Dexmedetomidina , Feminino , Humanos , Hipnóticos e Sedativos , Masculino , Éteres Metílicos , Propofol , Estudos Prospectivos , Sevoflurano
8.
Pediatr Transplant ; 20(8): 1098-1105, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27734600

RESUMO

Adults, older children, and adolescent patients with a BMI categorized as overweight or obese have decreased survival after HTx. Anthropometric correlates of survival after HTx in infants have not been well defined. In a retrospective analysis of the UNOS registry, patients age 0-24 months were classified according to the WHO height-for-age and weight-for-age norms, as well as arbitrary BMI-for-age percentiles. Outcomes of 1-year survival, conditional long-term survival, and cause-specific mortality were examined. Infants with stunted growth according to the WHO definition had increased risks of early mortality, late mortality, and death due to graft failure after HTx. Secondary analysis of first-year survival demonstrated increased mortality in children who were underweight according to weight-for-age, but a survival disadvantage in the highest BMI-for-age category, likely due to short recumbent length leading to relatively high BMI values. Stunted growth relative to WHO standards predicts mortality following heart transplant in children less than 2 years of age. The association between post-transplant mortality and high BMI-for-age, as demonstrated in older cohorts, was observed in the infant cohort only due to stunting, and not due to overweight classification.


Assuntos
Estatura , Peso Corporal , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Transplante de Coração , Antropometria , Índice de Massa Corporal , Pré-Escolar , Feminino , Insuficiência Cardíaca/cirurgia , Humanos , Lactente , Recém-Nascido , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
9.
J Extra Corpor Technol ; 48(3): 141-147, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27729708

RESUMO

Over the years, there has been a growing recognition of the potential negative sequelae of allogeneic blood products on postoperative outcomes following cardiac surgery. In addition, followers of the Jehovah's Witness (JW) faith have a religious restriction against receiving blood or blood components. Advances in perioperative care, cardiopulmonary bypass (CPB), and surgical technique have minimized the need for allogeneic blood products. Specific blood conservation strategies include maximizing the preoperative hematocrit and coagulation function as well as intraoperative strategies, such as acute normovolemic hemodilution and adjustments of the technique of CPB. We report a 7-month-old patient whose parents were of the JW faith who underwent a comprehensive stage II procedure for hypoplastic left heart syndrome without exposure to blood or blood products during his hospital stay. Perioperative techniques for blood avoidance are discussed with emphasis on their application to infants undergoing surgery for congenital heart disease.


Assuntos
Procedimentos Médicos e Cirúrgicos sem Sangue/ética , Procedimentos Médicos e Cirúrgicos sem Sangue/métodos , Procedimentos Cirúrgicos Cardíacos/ética , Síndrome do Coração Esquerdo Hipoplásico/terapia , Testemunhas de Jeová , Consentimento dos Pais/ética , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar/ética , Ponte Cardiopulmonar/métodos , Humanos , Síndrome do Coração Esquerdo Hipoplásico/diagnóstico , Recém-Nascido , Masculino , Resultado do Tratamento
10.
Nature ; 459(7243): 49-54, 2009 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-19424148

RESUMO

Observations made using large ground-based and space-borne telescopes have probed cosmic history from the present day to a time when the Universe was less than one-tenth of its present age. Earlier still lies the remaining frontier, where the first stars, galaxies and massive black holes formed. They fundamentally transformed the early Universe by endowing it with the first sources of light and chemical elements beyond the primordial hydrogen and helium produced in the Big Bang. The interplay of theory and upcoming observations promises to answer the key open questions in this emerging field.

11.
Nucleic Acids Res ; 41(6): 3924-36, 2013 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-23396443

RESUMO

Lens epithelium-derived growth factor (LEDGF/p75) tethers lentiviral preintegration complexes (PICs) to chromatin and is essential for effective HIV-1 replication. LEDGF/p75 interactions with lentiviral integrases are well characterized, but the structural basis for how LEDGF/p75 engages chromatin is unknown. We demonstrate that cellular LEDGF/p75 is tightly bound to mononucleosomes (MNs). Our proteomic experiments indicate that this interaction is direct and not mediated by other cellular factors. We determined the solution structure of LEDGF PWWP and monitored binding to the histone H3 tail containing trimethylated Lys36 (H3K36me3) and DNA by NMR. Results reveal two distinct functional interfaces of LEDGF PWWP: a well-defined hydrophobic cavity, which selectively interacts with the H3K36me3 peptide and adjacent basic surface, which non-specifically binds DNA. LEDGF PWWP exhibits nanomolar binding affinity to purified native MNs, but displays markedly lower affinities for the isolated H3K36me3 peptide and DNA. Furthermore, we show that LEDGF PWWP preferentially and tightly binds to in vitro reconstituted MNs containing a tri-methyl-lysine analogue at position 36 of H3 and not to their unmodified counterparts. We conclude that cooperative binding of the hydrophobic cavity and basic surface to the cognate histone peptide and DNA wrapped in MNs is essential for high-affinity binding to chromatin.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/química , Nucleossomos/química , DNA/química , DNA/metabolismo , Histonas/química , Histonas/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Modelos Moleculares , Nucleossomos/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína
12.
Nature ; 451(7182): 1082-4, 2008 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-18305539

RESUMO

Massive stars are very rare, but their extreme luminosities make them both the only type of young star we can observe in distant galaxies and the dominant energy sources in the Universe today. They form rarely because efficient radiative cooling keeps most star--forming gas clouds close to isothermal as they collapse, and this favours fragmentation into stars of one solar mass or lower. Heating of a cloud by accreting low-mass stars within it can prevent fragmentation and allow formation of massive stars, but the necessary properties for a cloud to form massive stars-and therefore where massive stars form in a galaxy--have not yet been determined. Here we show that only clouds with column densities of at least 1 g cm(-2) can avoid fragmentation and form massive stars. This threshold, and the environmental variation of the stellar initial mass function that it implies, naturally explain the characteristic column densities associated with massive star clusters and the difference between the radial profiles of Halpha and ultraviolet emission in galactic disks. The existence of a threshold also implies that the initial mass function should show detectable variation with environment within the Galaxy, that the characteristic column densities of clusters containing massive stars should vary between galaxies, and that star formation rates in some galactic environments may have been systematically underestimated.

13.
J Orthop ; 54: 10-21, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38524361

RESUMO

Background: The incidence and histological type of spinal cancer is diverse. It is our role as physicians to explore the epidemiology of spinal cancers so that several projections can be made. Resource allocation, cost analyses, and the requirement of rehabilitation facilities all need to be considered.The objective of this paper is to provide an account of the acute spinal oncological admissions to the National Spinal Injuries Unit (NSIU) in both 2010 and 2020 with the hypothesis that upward trends will be noted. Only by exemplifying this trend, will it highlight the need to give spinal cancer the attention it deserves in the Republic of Ireland. Methods: All patients who were to undergo spinal surgery for primary or metastatic spinal cancer in the Mater Misericordiae University Hospital (MMUH) in 2010 and 2020 were included in this retrospective cohort study. A list of medical record numbers (MRNs) for all patients who underwent spinal surgery in the MMUH were included. Data pertaining to patient demographics were noted. Results: 90 patients were included in this retrospective cohort study. 37 patients in 2010, had increased to 53 by 2020. Metastatic disease to the spine was still the most prominent reason for referral. The most common spinal region affected was the thoracic spine. Breast cancer was the most prevalent metastatic cancer to the spine in 2010. Lung cancer became the most prevalent by 2020. Posterior spinal fusion was the most frequent surgical procedure performed. The length of stay in higher care facilities decreased from 5.4 days in 2010, to 4 days in 2020. Decreased were also seen in the mean length of hospital stay, plummeting from 23.6 days in 2010, to 7.6 days in 2020. The same could not be said for the 30-day mortality rate, increasing from 5.4% in 2010, to 9.4% in 2020. Conclusion: The results of this study show a substantial rise in the incidence and prevalence of both primary and metastatic spinal disease here in Ireland. One can see clear improvements in operative technique, with less patients proceeding to higher levels of post-operative care, and earlier discharge times. This data can be used for future planning. The paper highlights the economic cost of spinal oncological care, but it also identifies key areas where preventative campaigns can be targeted.

14.
Cardiol Res ; 15(1): 12-17, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38464705

RESUMO

Background: Remimazolam is a benzodiazepine which, like midazolam, has sedative, anxiolytic, and amnestic properties. Ester metabolism results in a half-life of 5 - 10 min, a limited context sensitive half-life, and rapid recovery when the infusion is discontinued. Methods: Following the Institutional Review Board (IRB) approval, we performed a retrospective chart review of patients who received remimazolam in the cardiac catheterization, cardiac magnetic resonance imaging (MRI), and electrophysiology suites. The primary objective was to assess efficacy and safety. The secondary objective was to describe bolus and infusion dosing of remimazolam and the need for adjunctive agents to optimize procedural sedation conditions. Results: The study cohort included 26 patients with a median age of 18 years and a total of 33 anesthetic encounters. The most common procedures were endomyocardial biopsy or isolated hemodynamic assessment (right or left heart catheterization). Remimazolam was the primary agent for sedation in 82% of the procedures. The majority of cases (25 encounters, 76%) included a bolus dose of remimazolam prior to the start of an infusion. For those patients who received a starting bolus dose, dosing typically ranged between 30 and 110 µg/kg. Continuous infusion rates of remimazolam varied from 5 to 20 µg/kg/min. No adverse hemodynamic or respiratory effects were noted. Midazolam, fentanyl, and dexmedetomidine were the most frequently used adjunctive agents. One patient required transition to general anesthesia due to the need for a surgical intervention based on the findings of the cardiac catheterization. All other patients were effectively sedated. Conclusions: Our preliminary experience demonstrates that remimazolam effectively provided sedation for diagnostic and therapeutic cardiovascular procedures. Future studies are needed to further define dosing parameters for both bolus dosing and continuous infusion as well as to compare remimazolam to other commonly used for procedural sedation in patients with congenital and acquired heart disease.

15.
J Med Cases ; 15(1): 26-30, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38328811

RESUMO

Pain following thoracotomy is one of the most severe forms of postoperative pain. Post-thoracotomy pain may increase the risk of post-surgical pulmonary complications, postoperative mortality, prolong hospitalization, and increase utilization of healthcare resources. To mitigate these effects, anesthesia providers commonly employ continuous epidural infusions, paravertebral blocks, and systemic opioids for pain management and improvement of pulmonary mechanics. We report the use of a continuous erector spinae plane block (ESPB) via a peripheral nerve catheter for postoperative pain management of an 18-year-old patient who underwent complex aortic coarctation repair via lateral thoracotomy, aided by cardiopulmonary bypass. Continuous ESPB proved to be an acceptable alternative for postoperative pain control, producing a substantial multi-dermatomal sensory block, resulting in adequate pain control, reduced opioid consumption, and a potentially shorter hospital stay.

16.
Exp Dermatol ; 22(11): 767-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24118207

RESUMO

The Bcl-2 family member Mcl-1 is essential for melanoma survival; however, the influence of oncogenic BRAF signalling remains elusive. In this study, Mcl-1 splice variant expression was determined in a panel of melanoma cell lines in relation to BRAF mutational status. Mcl-1L mRNA expression was increased in melanoma cells compared with primary melanocytes with significantly increased mRNA and protein expression observed in BRAF(V600E) mutant melanoma cells. Although no change in Mcl-1S mRNA was observed, Mcl-1S protein expression also increased in BRAF mutant melanoma cells. Additionally, while over-expression of mutant BRAF(V600E) increased both Mcl-1L and Mcl-1S expression, inhibition of hyperactive BRAF signalling resulted in decreased Mcl-1L expression. These studies suggest that the regulation of Mcl-1 expression by BRAF signalling is increased by oncogenic activation of BRAF, revealing a mechanism of apoptotic resistance which may be overcome by the use of more specifically targeted Mcl-1 inhibitors.


Assuntos
Regulação Neoplásica da Expressão Gênica , Melanoma/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Proteínas Proto-Oncogênicas B-raf/metabolismo , Transdução de Sinais , Neoplasias Cutâneas/metabolismo , Apoptose , Linhagem Celular Tumoral , Humanos , Melanócitos/metabolismo , Melanoma/genética , Mutação , Neoplasias Cutâneas/genética , Melanoma Maligno Cutâneo
17.
Anal Biochem ; 442(1): 62-7, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23906642

RESUMO

Microarrays of peptide and recombinant protein libraries are routinely used for high-throughput studies of protein-protein interactions and enzymatic activities. Imaging mass spectrometry (IMS) is currently applied as a method to localize analytes on thin tissue sections and other surfaces. Here, we have applied IMS as a label-free means to analyze protein-peptide interactions in a microarray-based phosphatase assay. This IMS strategy visualizes the entire microarray in one composite image by collecting a predefined raster of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry spectra over the surface of the chip. Examining the bacterial tyrosine phosphatase YopH, we used IMS as a label-free means to visualize enzyme binding and activity with a microarrayed phosphopeptide library printed on chips coated with either gold or indium-tin oxide. Furthermore, we demonstrate that microarray-based IMS can be coupled with surface plasmon resonance imaging to add kinetic analyses to measured binding interactions. The method described here is within the capabilities of many modern MALDI-TOF instruments and has general utility for the label-free analysis of microarray assays.


Assuntos
Fosfopeptídeos/química , Análise Serial de Proteínas , Proteínas Tirosina Fosfatases/química , Ensaios de Triagem em Larga Escala , Espectrometria de Massas , Proteínas Tirosina Fosfatases/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Ressonância de Plasmônio de Superfície , Yersinia pestis/enzimologia
18.
J Clin Med Res ; 15(3): 174-180, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37035849

RESUMO

Remimazolam is a novel benzodiazepine with sedative and amnestic properties similar to midazolam. Ester metabolism results in a half-life of 5 - 10 min and a limited context sensitive half-life. We present preliminary retrospective experience with its use as a primary agent for procedural sedation for brief invasive and noninvasive procedures. The study cohort included seven patients, ranging in age from 14 to 51 years. Remimazolam administration included bolus dosing in two patients and a combination of bolus dosing followed by an infusion in the other five patients. The initial bolus dose of remimazolam ranged from 2.5 to 5 mg. Starting doses for the infusion ranged from 10 to 30 µg/kg/min with titration of the continuous infusion during the procedure, ranging from 10 - 30 µg/kg/min. Median dose infusion requirements were 15 - 20 µg/kg/min. One procedure was completed with remimazolam as the sole anesthetic agent while the other six patients received adjunctive agents. Changes in blood pressure or oxygen saturation were noted which resolved with minimal interventions such as a decrease in remimazolam infusion rate or an increase in supplemental oxygen administration. Our anecdotal experience provides further support for the efficacy of remimazolam as an agent for procedural sedation.

19.
Cardiol Res ; 14(1): 86-90, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36896227

RESUMO

General anesthesia or procedural sedation may be required to ensure immobility, facilitate completion of the procedure, and ensure patient comfort during diagnostic or therapeutic procedures in the cardiac catheterization suite. Although propofol and dexmedetomidine are two of the more commonly chosen agents, concerns regarding their impact on inotropic, chronotropic or dromotropic function may limit their applicability based on underlying patient comorbid conditions. We present three patients with comorbid conditions involving pacemaker (natural or implanted) function or cardiac conduction which impacted the choice of agent for procedural sedation during procedures in the cardiac catheterization suite. Remimazolam, a novel ester-metabolized benzodiazepine, was used as the primary agent for sedation in an effort to limit detrimental effects on chronotropic and dromotropic function which may be seen with propofol or dexmedetomidine. Remimazolam's potential utility in procedural sedation is discussed, previous reports of its use are reviewed, and dosing algorithms are presented.

20.
Cureus ; 15(7): e42295, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37609096

RESUMO

INTRODUCTION:  Accurate medical documentation is important in the perioperative period, ensuring the safe transfer of information between teams involved in the surgical patient's care. This has been highlighted by multiple standards of care guidelines within the United Kingdom. The use of standardized pre-templated documents has displayed significant success in minimizing errors during the admission and operative stages. The aim of this study is to evaluate whether a similar proforma for the post-operative stage is successful in orthopedic patients. METHODS:  A retrospective review of 25 consecutive orthopedic elective patients was conducted during the first cycle. Exclusion criteria included patients who were under 16, day case procedures, and admission due to trauma. The second cycle consisted of a prospective review of 25 patients a month following the implementation of the new proforma. Both cycles were scored against 10 inclusion parameters as outlined by national guidelines. RESULTS:  Implementation of the proforma resulted in a significant improvement in post-operative note compliance. A total of six parameters showed a statistically significant improvement (p<0.05). This included wound assessment (58.3%-100%, p<0.001), post-operative imaging (37.5%-92%, p<0.001), neurovascular assessment (83.3%-100%, p=0.017), National Early Warning Score (25.0%-100%, p<0.001), venous thromboembolism prophylaxis (29.2%-96.0%, p<0.001), and antibiotic administration (4.2%-84.0%, p<0.001). CONCLUSIONS:  Monitoring of important clinical parameters significantly improved following the implementation of the post-operative proforma. These results will hopefully cause the introduction of other proformas in other surgical specialties and other units.

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