Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 67
Filtrar
Mais filtros

Bases de dados
Tipo de documento
Intervalo de ano de publicação
1.
Proc Natl Acad Sci U S A ; 119(43): e2205417119, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36256820

RESUMO

Antigen-specific therapies hold promise for treating autoimmune diseases such as multiple sclerosis while avoiding the deleterious side effects of systemic immune suppression due to delivering the disease-specific antigen as part of the treatment. In this study, an antigen-specific dual-sized microparticle (dMP) treatment reversed hind limb paralysis when administered in mice with advanced experimental autoimmune encephalomyelitis (EAE). Treatment reduced central nervous system (CNS) immune cell infiltration, demyelination, and inflammatory cytokine levels. Mechanistic insights using single-cell RNA sequencing showed that treatment impacted the MHC II antigen presentation pathway in dendritic cells, macrophages, B cells, and microglia, not only in the draining lymph nodes but also strikingly in the spinal cord. CD74 and cathepsin S were among the common genes down-regulated in most antigen presenting cell (APC) clusters, with B cells also having numerous MHC II genes reduced. Efficacy of the treatment diminished when B cells were absent, suggesting their impact in this therapy, in concert with other immune populations. Activation and inflammation were reduced in both APCs and T cells. This promising antigen-specific therapeutic approach advantageously engaged essential components of both innate and adaptive autoimmune responses and capably reversed paralysis in advanced EAE without the use of a broad immunosuppressant.


Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Animais , Camundongos , Antígenos , Citocinas , Camundongos Endogâmicos C57BL , Paralisia , Catepsinas , Imunossupressores/uso terapêutico
2.
Immunity ; 43(2): 354-68, 2015 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-26231117

RESUMO

Type 2 innate lymphoid cells (ILC2s) promote anti-helminth responses and contribute to allergies. Here, we report that Bcl11b, previously considered a T-cell-specific transcription factor, acted directly upstream of the key ILC2 transcription factor Gfi1 to maintain its expression in mature ILC2s. Consequently, Bcl11b(-/-) ILC2s downregulated Gata3 and downstream genes, including Il1rl1 (encoding IL-33 receptor), and upregulated Rorc and type 3 ILC (ILC3) genes. Additionally, independent of Gfi1, Bcl11b directly repressed expression of the gene encoding the ILC3 transcription factor Ahr, further contributing to silencing of ILC3 genes in ILC2s. Thus, Bcl11b(-/-) ILC2s lost their functions and gained ILC3 functions, and although they expanded in response to the protease allergen papain, they produced ILC3 but not ILC2 cytokines and caused increased airway infiltration of neutrophils instead of eosinophils. Our results demonstrate that Bcl11b is more than just a T-cell-only transcription factor and establish that Bcl11b sustains mature ILC2 genetic and functional programs and lineage fidelity.


Assuntos
Citrobacter rodentium/imunologia , Infecções por Enterobacteriaceae/imunologia , Eosinófilos/imunologia , Subpopulações de Linfócitos/imunologia , Linfócitos/imunologia , Neutrófilos/imunologia , Proteínas Repressoras/metabolismo , Células Th2/imunologia , Proteínas Supressoras de Tumor/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Diferenciação Celular , Linhagem da Célula , Movimento Celular/genética , Células Cultivadas , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/metabolismo , Regulação da Expressão Gênica/genética , Imunidade Inata , Proteína 1 Semelhante a Receptor de Interleucina-1 , Camundongos , Camundongos Endogâmicos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Receptores de Hidrocarboneto Arílico/genética , Receptores de Interleucina/genética , Proteínas Repressoras/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/genética
3.
World J Urol ; 41(12): 3759-3764, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37845553

RESUMO

PURPOSE: Ureteric stents placed after ureteroscopy typically require cystoscopy for removal. Stent extraction strings allow the option of patient self-removal. This facilitates shorter stent dwell time, and cost-savings. Concerns regarding safety and limited evidence regarding patient acceptability are speculated reasons for infrequent clinical use of extraction strings. This study investigates our recent experience using routine self-removal of stents on extraction strings to provide evidence to address these concerns. METHODS: In February 2020, our hospital adopted a policy for self-removal of stents on extraction strings to be routine following ureteroscopy. This was influenced by motivation to improve service capacity for diagnostic flexible cystoscopy, hospital avoidance during the pandemic, perceived improvement for the patient experience, and cost-saving. Prospective clinical and patient-reported outcome data were collected and evaluated. RESULTS: There were 168 patients who had stents on extraction strings. Mean stent dwell time was 5.2 ± 1.8 days. Primary ureteroscopy was performed in 40.5%, and 59.5% had procedures using an access sheath. Self-removal at home was successful for 79% of patients. Stent dislodgement rate was 3.0% (5/168) and retained stents due to string detachment occurred in 1.8% (3/168). Almost all indicated they "would remove the stent on string again" (90%, 128/142) and the majority reported stent removal as "very easy" (61%, 87/142). Cost modelling estimates a total saving of AUD $148,869 per annum for routine use of extraction strings at our hospital. CONCLUSION: Our experience reflects that stent extraction strings may be used routinely with acceptable low complication rates, favourable patient experiences and associated cost savings.


Assuntos
Ureter , Masculino , Humanos , Ureter/cirurgia , Estudos Prospectivos , Ureteroscopia , Remoção de Dispositivo/métodos , Stents
4.
Langenbecks Arch Surg ; 408(1): 173, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37133529

RESUMO

PURPOSE: Pelvic exenteration (PE) involves radical surgical resection of pelvic organs and is associated with considerable morbidity. Sarcopenia is recognised as a predictor of poor surgical outcomes. This study aimed to determine if preoperative sarcopenia is associated with postoperative complications after PE surgery. METHODS: This retrospective study included patients who underwent PE with an available preoperative CT scan between May 2008 and November 2022 at the Royal Adelaide Hospital and St. Andrews Hospital in South Australia. Total Psoas Area Index (TPAI) was estimated by measuring the cross-sectional area of the psoas muscles at the level of the third lumbar vertebra on abdominal CT, normalised for patient height. Sarcopenia was diagnosed based on gender-specific TPAI cut-off values. Logistic regression analyses were performed to identify risk factors for major postoperative complications with a Clavien-Dindo (CD) grade ≥ 3. RESULTS: In total, 128 patients who underwent PE were included, 90 of whom formed the non-sarcopenic group (NSG) and 38 the sarcopenic group (SG). Major postoperative complications (CD grade ≥ 3) occurred in 26 (20.3%) patients. There was no detectable association with sarcopenia and an increased risk of major postoperative complications. Preoperative hypoalbuminemia (P = 0.01) and a prolonged operative time (P = 0.002) were significantly associated with a major postoperative complication on multivariate analysis. CONCLUSION: Sarcopenia is not a predictor of major postoperative complications in patients undergoing PE surgery. Further efforts aimed specifically at optimising preoperative nutrition may be warranted.


Assuntos
Exenteração Pélvica , Sarcopenia , Humanos , Sarcopenia/complicações , Sarcopenia/diagnóstico por imagem , Estudos Retrospectivos , Exenteração Pélvica/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Músculos Psoas/diagnóstico por imagem , Músculos Psoas/patologia , Fatores de Risco
5.
J Pharm Technol ; 38(1): 18-25, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35141723

RESUMO

Background: Penicillin allergy is one of the most frequent self-reported allergies; however, only about 10% of reported allergies are accurate. Objectives: Through the creation of a continuing pharmacy education (CPE) activity, we sought to assess knowledge gaps and comfort levels in the management of penicillin allergies. Methods: A 1-hour enduring-content CPE activity was offered as an interactive course from September 20, 2019, to September 20, 2020. Participants completed 3 surveys (pre-survey, post-survey, and follow-up survey). Participants were pharmacists and pharmacy technicians who completed, at a minimum, the activity and both pre- and post-surveys. The primary outcome was the percentage of participants scoring >80% on knowledge-based questions on the post-survey compared with the pre-survey. Secondary outcomes included pre-post comparisons on knowledge-based questions, participants' self-report of an allergy, and comfort levels dispensing cephalosporins in a patient with a self-reported penicillin allergy. Results: A total of 389 participants completed the CPE activity, with 176 included for analysis. Significantly more participants scored >80% on knowledge-based questions on the post-survey compared with the pre-survey (71.6% vs 22.7%, P < .001). There was no significant difference between the percentage of participants scoring >80% on the post-survey and the follow-up survey (71.6% vs 65%, P = .119). The majority of participants (74%) felt comfortable dispensing a cephalosporin in a patient with a penicillin allergy on the pre-survey, with similar percentages on the post- and follow-up surveys (77% and 90%, respectively). Conclusion: A targeted continuing education program improved overall knowledge, which was sustained for up to 2 months.

6.
Biochemistry ; 58(16): 2167-2175, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-30907577

RESUMO

The sodium-pumping NADH:quinone oxidoreductase (Na+-NQR) is a bacterial enzyme that oxidizes NADH, reduces ubiquinone, and translocates Na+ across the membrane. We previously identified three acidic residues in the membrane-spanning helices, near the cytosol, NqrB-D397, NqrD-D133, and NqrE-E95, as candidates likely to be involved in Na+ uptake, and replacement of any one of them by a non-acidic residue affects the Na+-dependent kinetics of the enzyme. Here, we have inquired further into the role of the NqrE-E95 residue by constructing a series of mutants in which this residue is replaced by amino acids with charges and/or sizes different from those of the glutamate of the wild-type enzyme. All of the mutants showed altered steady-state kinetics with the acceleration of turnover by Na+ greatly diminished. Selected mutants were studied by other physical methods. Membrane potential measurements showed that NqrE-E95D and A are significantly less efficient in ion transport. NqrE-E95A, Q, and D were studied by transient kinetic measurements of the reduction of the enzyme by NADH. In all three cases, the results indicated inhibition of the electron-transfer step in which the FMNC becomes reduced. This is the first Na+-dependent step and is associated with Na+ uptake by the enzyme. Electrochemical measurements on NqrE-E95Q showed that the Na+ dependence of the redox potential of the FMN cofactors has been lost. The fact that the mutations at the NqrE-E95 site have specific effects related to translocation of Na+ and Li+ strongly indicates a definite role for NqrE-E95 in the cation transport process of Na+-NQR.


Assuntos
Proteínas de Bactérias/metabolismo , Ácido Glutâmico/metabolismo , NADH NADPH Oxirredutases/metabolismo , Quinona Redutases/metabolismo , Sódio/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Membrana Celular/metabolismo , Ácido Glutâmico/química , Ácido Glutâmico/genética , Transporte de Íons/genética , Cinética , Modelos Moleculares , Mutação de Sentido Incorreto , NADH NADPH Oxirredutases/química , NADH NADPH Oxirredutases/genética , Conformação Proteica , Quinona Redutases/química , Quinona Redutases/genética , Vibrio cholerae/enzimologia , Vibrio cholerae/genética
7.
Proc Natl Acad Sci U S A ; 113(27): 7608-13, 2016 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-27330109

RESUMO

Invariant natural killer T (iNKT) cells are innate-like T cells that recognize glycolipid antigens and play critical roles in regulation of immune responses. Based on expression of the transcription factors (TFs) Tbet, Plzf, and Rorγt, iNKT cells have been classified in effector subsets that emerge in the thymus, namely, iNKT1, iNKT2, and iNKT17. Deficiency in the TF Bcl11b in double-positive (DP) thymocytes has been shown to cause absence of iNKT cells in the thymus and periphery due to defective self glycolipid processing and presentation by DP thymocytes and undefined intrinsic alterations in iNKT precursors. We used a model of cre-mediated postselection deletion of Bcl11b in iNKT cells to determine its intrinsic role in these cells. We found that Bcl11b is expressed equivalently in all three effector iNKT subsets, and its removal caused a reduction in the numbers of iNKT1 and iNKT2 cells, but not in the numbers of iNKT17 cells. Additionally, we show that Bcl11b sustains subset-specific cytokine production by iNKT1 and iNKT2 cells and restricts expression of iNKT17 genes in iNKT1 and iNKT2 subsets, overall restraining the iNKT17 program in iNKT cells. The total numbers of iNKT cells were reduced in the absence of Bcl11b both in the thymus and periphery, associated with the decrease in iNKT1 and iNKT2 cell numbers and decrease in survival, related to changes in survival/apoptosis genes. Thus, these results extend our understanding of the role of Bcl11b in iNKT cells beyond their selection and demonstrate that Bcl11b is a key regulator of iNKT effector subsets, their function, identity, and survival.


Assuntos
Células T Matadoras Naturais/fisiologia , Proteínas Repressoras/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Citocinas/metabolismo , Regulação da Expressão Gênica , Camundongos , Neuropilina-1/metabolismo , Timo/imunologia
10.
J Antimicrob Chemother ; 73(8): 2252-2258, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29846603

RESUMO

Background: Pharmacists are key members of antimicrobial stewardship (AS) teams. It is unknown if and how US colleges and schools of pharmacy incorporate AS into their Doctor of Pharmacy (PharmD) curricula. Methods: This study was a cross-sectional, multicentre, electronic survey distributed to infectious diseases faculty or department chairs of 137 accredited and candidate-status PharmD programmes. Results: One hundred and sixteen programmes participated, representing an 84.7% response rate. AS education was integrated into the required didactic, elective didactic and experiential education components of the curricula in 79 (68.1%), 43 (37.1%) and 97 (83.6%) PharmD programmes, respectively. The most common AS topics in required and elective didactic curricula were AS definitions, principles and purpose (98.7% and 86.0%) and the pharmacist's role in AS (93.7% and 83.7%). In the required and elective didactic curricula, lecture (93.7% and 86.0%) and case-based instruction (57.0% and 83.7%) were the most common instructional methods. For experiential education, the pharmacist's role in AS (96.9%), de-escalation of antimicrobials (96.9%) and antimicrobial dose optimization (95.9%) were the most common AS topics. PharmD programmes employing a faculty member who specializes in AS were more likely to offer AS experiential education than programmes without AS faculty (88.1% versus 71.9%, P = 0.049). Conclusions: Integration of AS education in US PharmD curricula is variable and there are considerable differences in the AS activities and topics delivered. PharmD programmes should attempt to expose students to AS education to prepare future pharmacists for AS practice. Efforts should be made to incorporate interprofessional collaboration into AS education.


Assuntos
Gestão de Antimicrobianos/métodos , Currículo/estatística & dados numéricos , Educação Médica/métodos , Faculdades de Farmácia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos e Questionários , Adulto Jovem
11.
BJU Int ; 122 Suppl 5: 15-21, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30370984

RESUMO

OBJECTIVE: To assess the clinical utility of systematic Doppler ultrasonography (DUS) after robot-assisted partial nephrectomy (PN) for the detection of renal artery pseudoaneurysm (PA) and to allow pre-emptive arterial embolization to reduce the postoperative bleeding risk. MATERIALS AND METHODS: A retrospective study was conducted including all consecutive patients treated with robot-assisted PN for renal tumours between 2015 and 2017. Every patient underwent renal DUS in the early postoperative period. The presence of PA, arteriovenous malformation or collection on the DUS, as well as the incidence of haemorrhagic complications and need for transfusion/embolization were assessed. RESULTS: Eighty-three patients were included, with a median (range) age of 58 (19-80) years. The median (range) follow-up was 5 (1-30) months. The mean (±sd) tumour size was 31 (±13.1) mm, the median (range) RENAL nephrometry score was 6 (4-11), and the mean (±sd) warm ischaemia time was 22 (±7) min. A haemostatic agent was used in 12 patients (14.5%). No patient encountered haemorrhagic complications postoperatively, and no patient required transfusion. The median (interquartile range) time to DUS postoperatively was 7 (6-8) days. DUS revealed one asymptomatic PA (1.2%), which was treated with pre-emptive embolization. This was the only patient who encountered a Clavien grade III complication, while 20 patients (24%) had a complication grade I/II. CONCLUSIONS: No haemorrhagic complications occurred in the present study population, although one asymptomatic PA was found. It was diagnosed early with DUS, allowing pre-emptive management with embolization. These results suggest the potential clinical utility of early postoperative DUS in order to screen for PA to reduce the risk of post-PN haemorrhagic complications.


Assuntos
Falso Aneurisma/diagnóstico por imagem , Neoplasias Renais/cirurgia , Nefrectomia/efeitos adversos , Hemorragia Pós-Operatória/prevenção & controle , Ultrassonografia Doppler em Cores , Adulto , Idoso , Falso Aneurisma/complicações , Falso Aneurisma/terapia , Diagnóstico Precoce , Embolização Terapêutica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Hemorragia Pós-Operatória/etiologia , Período Pós-Operatório , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Adulto Jovem
12.
Ann Pharmacother ; 52(8): 769-779, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29514462

RESUMO

OBJECTIVE: To review the pharmacology, spectrum of activity, pharmacokinetics, pharmacodynamics, safety, efficacy, administration, and considerations for clinical use of meropenem/vaborbactam (M/V). DATA SOURCES: A literature search using PubMed and clinicaltrials.gov (June 2013 to December 2017) was conducted using the search terms meropenem, vaborbactam, RPX7009, biapenem, RPX2003, and carbavance. References from relevant articles and conference abstracts were also reviewed. STUDY SELECTION AND DATA EXTRACTION: Preclinical, phase I studies, and phase III studies written in the English language were evaluated. DATA SYNTHESIS: M/V is a novel carbapenem/ß-lactamase inhibitor antimicrobial with in vitro activity against nearly 99% of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae. M/V is approved for the treatment of adults with complicated urinary tract infections (cUTIs), including pyelonephritis. In a phase III cUTI trial (TANGO I), 98.4% of patients treated with M/V experienced overall clinical success compared with 94% of patients treated with piperacillin/tazobactam (95% CI = 0.7 to 9.1). When compared with best available therapy for carbapenem-resistant Enterobacteriaceae (CRE) infections in TANGO II, patients receiving M/V were more likely to achieve clinical cure at both the end of therapy (64.3% vs 33.3%, P = 0.04) as well as at the test of cure (57.1% vs 26.7%, P = 0.04). The most common adverse effects associated with M/V were headache, infusion-site reactions, and diarrhea. CONCLUSION: M/V has a valuable role in the treatment of CRE and should be used judiciously to preserve its use for resistant infections.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Ácidos Borônicos/uso terapêutico , Meropeném/uso terapêutico , Animais , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Ácidos Borônicos/química , Ácidos Borônicos/farmacocinética , Ácidos Borônicos/farmacologia , Humanos , Meropeném/química , Meropeném/farmacocinética , Meropeném/farmacologia
13.
Ann Clin Microbiol Antimicrob ; 17(1): 37, 2018 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-30309347

RESUMO

BACKGROUND: Clostridium difficile-associated diarrhea (CDAD) is a major public health threat that results in increased length of stay, hospital readmissions, deaths, and economic burden. CDAD treatment is often guided by severity of disease. Although various tools exist to determine CDAD severity, real-world data evaluating the use of such tools in treatment algorithms are sparse. METHODS: A local CDAD treatment pathway was developed independently to guide fidaxomicin prescribing at wellStar Health System (WellStar) and at Lee Health (LH) and Sarasota Memorial Hospital (SMH). Each algorithm was designed locally by the stewardship pharmacist and was utilized to identify patients at high risk for C. difficile recurrence. Patient and clinical data was retrospectively gathered to evaluate the utility and outcomes of the treatment pathway. RESULTS: There were 262 patients that received fidaxomicin at these three hospitals during the study time period. Only 30% at WellStar and 20% at LH or SMH met the study criteria and adhered to the pathway requirements. After completion of fidaxomicin, 30-day recurrence rates at WellStar was 0 and at LH and SMH 7%. Clinical cure rates were 83% in WellStar and 93% in LH and SMH. CONCLUSIONS: The results from these two pathways show positive outcomes for the use of fidaxomicin in patients at high risk for CDAD recurrence. This data supports the potential utility of fidaxomicin against CDAD.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Clostridium/tratamento farmacológico , Fidaxomicina/uso terapêutico , Pacientes Internados/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sudeste dos Estados Unidos/epidemiologia
14.
Consult Pharm ; 33(2): 89-97, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29409575

RESUMO

OBJECTIVE: To review the pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, tolerability, dosing, and administration of bezlotoxumab (BEZ), as well as its place in the prevention of Clostridium difficile infection (CDI) recurrence. DATA SOURCES: A search of PubMed and Google Scholar using the terms "bezlotoxumab," "CDB1," "MDX-1388," and "MK-6072" was performed. The manufacturer's website was also reviewed to further identify relevant information. STUDY SELCTION: All English-language articles from 2006 to May 2017 appearing in these searches were reviewed for relevance to this paper. In addition, their bibliographies were reviewed to identify any articles not identified in the searches. DATA SYNTHESIS: BEZ is a human monoclonal antibody that binds to Clostridium difficile toxin B. It is approved by the Food and Drug Administration to reduce CDI recurrence in adult patients who are receiving antibiotic therapy for CDI and are at high risk for CDI recurrence. It is given as a single dose of 10 mg/kg via an intravenous infusion. It is eliminated by catabolism. Phase III clinical trials demonstrated that BEZ was associated with significantly lower rates of CDI recurrence, compared with placebo. The most common adverse events reported during clinical trials were diarrhea and nausea. There is a warning regarding the use of BEZ in patients with a history of congestive heart failure. The most common adverse reactions associated with BEZ are nausea, pyrexia, and headache. CONCLUSION: BEZ has been proven safe and effective in preventing CDI recurrence. Given its high cost, it should be reserved for patients at high risk for CDI recurrence.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Neutralizantes/administração & dosagem , Clostridioides difficile/efeitos dos fármacos , Infecções por Clostridium/prevenção & controle , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Anticorpos Neutralizantes/efeitos adversos , Anticorpos Neutralizantes/farmacologia , Proteínas de Bactérias/imunologia , Toxinas Bacterianas/imunologia , Anticorpos Amplamente Neutralizantes , Humanos , Infusões Intravenosas , Prevenção Secundária/métodos
15.
Surg Endosc ; 29(7): 1709-13, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25294546

RESUMO

BACKGROUND: Wound complications including infection and necrosis remain common during complex open ventral hernia repair. Advancements or enhancements in imaging technology may abate some of these issues but requires more investigation. Laser-assisted fluorescent imaging with indocyanine green (Spy Elite, LifeCell Corporation, Branchburg, NJ) allows visualization and quantification of perfusion, facilitating management of poorly perfused tissue. METHODS: Ten patients, who underwent large or massive ventral or incisional hernia repair with biologic graft reinforcement and either perforator-sparing components separation or primary open repair, underwent intraoperative laser-assisted fluorescent imaging with indocyanine green from August 2012 to August 2013. The cases were reviewed by an independent data collector with primary outcomes of postoperative skin infection and/or abdominal wall necrosis. RESULTS: Three (30%) patients had adequate perfusion, while seven (70%) patients had inadequate skin perfusion and necessitated excision of additional tissue. Of the patients whose ischemic tissue was removed, four (57%) patients had an infection and no patients developed necrosis postoperatively. Of the patients who had no removal of additional skin, one (33%) patient developed an infection and one (33%) patients developed skin necrosis. CONCLUSION: The intraoperative use of laser-assisted fluorescent imaging with indocyanine green may change management of abdominal wall flaps, even in perforator-sparing operations. Our study series is small and cannot suggest statistical significance in the potential benefit of intraoperative imaging, but shows that up to 70% of patients may require change in management due to poorly perfused tissue flaps.


Assuntos
Parede Abdominal/cirurgia , Angiofluoresceinografia/métodos , Hérnia Ventral/cirurgia , Herniorrafia/métodos , Verde de Indocianina , Retalhos Cirúrgicos , Corantes , Feminino , Hérnia Ventral/diagnóstico , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade
16.
Hosp Pharm ; 50(11): 978-84, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27621505

RESUMO

BACKGROUND: Leadership is considered a professional obligation for all pharmacists. It is important to integrate leadership training in residency programs to meet the leadership needs and requirements of the profession. OBJECTIVE: To evaluate the importance of leadership development during postgraduate year 1 (PGY1) pharmacy practice residency training as perceived by new practitioners. METHODS: A 15-question online survey was distributed to residency-trained new practitioners to assess (1) amount of time dedicated to leadership training during residency training, (2) different leadership tools utilized, (3) residents' participation in various committees or councils, (4) perceived benefit of increased leadership training, (5) importance of having a mentor, (6) understanding of the residency organization's strategic objectives, (7) discussion of Pharmacy Practice Model Initiative (PPMI) during residency training, and (8) adequacy of leadership training in preparation to become a pharmacy practice leader. RESULTS: Although the majority of resident respondents had less than 20% of their residency devoted to leadership, nearly all survey participants acknowledged that leadership is an important component of PGY1 residency training. Residents agreed that their residency experience would have benefited from increased leadership opportunities. Most residents were knowledgeable about their organization's strategic objectives but did not have a full understanding of pharmacy initiatives such as the PPMI. CONCLUSION: Feedback from residents indicates that an optimal dedication to leadership training would range between 20% and 30% of the residency year. Increased focus on PPMI, mentorship, and expanded use of leadership tools can serve as a way to help meet the future leadership needs of the pharmacy profession and help to better prepare residents to become pharmacy practice leaders.

17.
J Biol Chem ; 288(43): 31241-9, 2013 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-24030824

RESUMO

The Na(+)-pumping NADH:quinone complex is found in Vibrio cholerae and other marine and pathogenic bacteria. NADH:ubiquinone oxidoreductase oxidizes NADH and reduces ubiquinone, using the free energy released by this reaction to pump sodium ions across the cell membrane. In a previous report, a conserved aspartic acid residue in the NqrB subunit at position 397, located in the cytosolic face of this protein, was proposed to be involved in the capture of sodium. Here, we studied the role of this residue through the characterization of mutant enzymes in which this aspartic acid was substituted by other residues that change charge and size, such as arginine, serine, lysine, glutamic acid, and cysteine. Our results indicate that NqrB-Asp-397 forms part of one of the at least two sodium-binding sites and that both size and charge at this position are critical for the function of the enzyme. Moreover, we demonstrate that this residue is involved in cation selectivity, has a critical role in the communication between sodium-binding sites, by promoting cooperativity, and controls the electron transfer step involved in sodium uptake (2Fe-2S → FMNC).


Assuntos
Proteínas de Bactérias/metabolismo , Quinona Redutases/metabolismo , Sódio/metabolismo , Vibrio cholerae/enzimologia , Substituição de Aminoácidos , Ácido Aspártico/química , Ácido Aspártico/genética , Ácido Aspártico/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Sítios de Ligação , Transporte de Elétrons/fisiologia , Transporte de Íons/fisiologia , Mutação de Sentido Incorreto , Quinona Redutases/química , Quinona Redutases/genética , Sódio/química , Vibrio cholerae/genética
19.
Mil Med ; 188(9-10): e3265-e3268, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-36355858

RESUMO

Dieulafoy's lesions (DLs) are a rare and difficult-to-identify cause of acute gastrointestinal bleeding that can lead to hemorrhagic shock. We present a case of a 23-year-old previously healthy male presenting with melenic stools and hemorrhagic shock. Computed tomography of abdomen and pelvis with oral and intravenous contrast showed a possible source of hemorrhage as a hyperdense intraluminal material within the stomach. Initial urgent esophagogastroduodenoscopy showed a large, nonbleeding distal esophageal DL, which was treated successfully with 10 mL of 1:10,000 epinephrine and bipolar cauterization with 10 Fr Gold Probe™. Hemorrhage recurred 2 d later, prompting another esophagogastroduodenoscopy, which found another DL within the gastric fundus. Treatment with epinephrine, Gold Probe™, and through-the-scope Hemoclips was unsuccessful because of difficult visualization and positioning. A subsequent attempt was made using the over-the-scope clip (OTSC) Padlock™ Clip Defect Closure System with successful hemostasis and stabilization of the patient. His hospital course was complicated by left lower lobe segmental pulmonary embolism without right heart strain for which he was discharged on 3 months of anticoagulation with apixaban. On follow-up, there was no recurrence of gastrointestinal bleeding (GIB) despite 3 months of anticoagulation. He did not complete the Basic Underwater Demolition/SEAL (BUD/S) Training. This case report demonstrates the evaluation and management of a patient with hemorrhagic shock from two DLs and sustained hemostasis with the Padlock™ OTSC in the setting of apixaban anticoagulation.


Assuntos
Hemostase Endoscópica , Choque Hemorrágico , Humanos , Masculino , Adulto Jovem , Adulto , Hemostase Endoscópica/efeitos adversos , Hemostase Endoscópica/métodos , Fundo Gástrico/cirurgia , Fundo Gástrico/patologia , Choque Hemorrágico/complicações , Choque Hemorrágico/terapia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , Epinefrina , Coagulação Sanguínea , Anticoagulantes
20.
ANZ J Surg ; 93(10): 2450-2456, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37132091

RESUMO

INTRODUCTION: The ideal method for urinary diversion following total pelvic exenteration (TPE) remains unclear. This study compares the outcomes of double-barrelled uro-colostomy (DBUC) and ileal conduit (IC) in a single Australian centre. METHODS: All consecutive patients who underwent pelvic exenteration with the formation of either a DBUC or an IC between 2008 and November 2022 were identified from the prospective database from the Royal Adelaide Hospital and St. Andrews Hospital. Demographic, operative characteristics, general perioperative, long-term urological and other relevant surgical complications were compared via univariate analyses. RESULTS: Of 135 patients undergoing exenteration, 39 patients were eligible for inclusion: 16 patients with a DBUC, and 23 patients with an IC. More patients in the DBUC group had previous radiotherapy (93.8% vs. 65.2%, P = 0.056) and flap pelvic reconstruction (93.7% vs. 45.5%, P = 0.002). The rate of ureteric stricture trended higher in the DBUC group (25.0% vs. 8.7%, P = 0.21), but in contrast, urine leak (6.3% vs. 8.7%, P>0.999), urosepsis (43.8% vs. 60.9%, P = 0.29), anastomotic leak (0.0% vs. 4.3%, P>0.999), and stomal complications requiring repair (6.3% vs. 13.0%, P = 0.63) trended lower. These differences were not statistically significant. Rates of grade III or greater complications were similar; however, no patients in the DBUC group died within 30-days or had grade IV complications requiring ICU admission compared with two deaths and one grade IV complication in the IC group. CONCLUSION: DBUC is a safe alternative to IC for urinary diversion following TPE, with potentially fewer complications. Quality of life and patient-reported outcomes are required.


Assuntos
Exenteração Pélvica , Derivação Urinária , Humanos , Colostomia/métodos , Exenteração Pélvica/efeitos adversos , Exenteração Pélvica/métodos , Qualidade de Vida , Austrália/epidemiologia , Derivação Urinária/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA